KR101862080B1 - 마이크로 rna 를 유효 성분으로 포함하는 암 치료용 약학 조성물 - Google Patents

마이크로 rna 를 유효 성분으로 포함하는 암 치료용 약학 조성물 Download PDF

Info

Publication number
KR101862080B1
KR101862080B1 KR1020160022462A KR20160022462A KR101862080B1 KR 101862080 B1 KR101862080 B1 KR 101862080B1 KR 1020160022462 A KR1020160022462 A KR 1020160022462A KR 20160022462 A KR20160022462 A KR 20160022462A KR 101862080 B1 KR101862080 B1 KR 101862080B1
Authority
KR
South Korea
Prior art keywords
mir
hsa
cancer
mirna
rna
Prior art date
Application number
KR1020160022462A
Other languages
English (en)
Other versions
KR20160103949A (ko
Inventor
이태우
심상형
유웅식
박한오
Original Assignee
(주)바이오니아
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by (주)바이오니아 filed Critical (주)바이오니아
Publication of KR20160103949A publication Critical patent/KR20160103949A/ko
Application granted granted Critical
Publication of KR101862080B1 publication Critical patent/KR101862080B1/ko

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C12N2310/141—MicroRNAs, miRNAs

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

본 발명은 miR-3670, miR-4477a, miR-8078 로 구성된 군에서 선택되는 하나 이상의 miRNA를 유효 성분으로 포함하는 암 치료용 약학 조성물에 관한 것이다. 본 발명에 따른 암 치료용 약학 조성물은 암 세포의 증식 억제 및 사멸을 유발하는 효과가 우수하다. 따라서 본 발명의 약학 조성물은 항암 치료제로서 유용하게 사용될 수 있다.

Description

마이크로 RNA 를 유효 성분으로 포함하는 암 치료용 약학 조성물{Pharmaceutical composition for treating cancer comprising miRNA}
본 발명은 이중 가닥 miRNA를 유효 성분으로 포함하여 항암제로 사용되는 약학 조성물에 관한 것이다. 보다 구체적으로, 본 발명은 암 세포의 증식을 효과적으로 억제하거나 암 세포의 자발적 사멸을 유도하는 방식을 특징으로 하는 miR-3670, miR-4477a, miR-8078 를 약제적 유효 성분으로 하고, 약학적으로 허용되는 담체를 포함하는 항암 약학 조성물에 관한 것이다.
유전자의 정상적인 제어가 이루어지지 않아 발생하는 질병, 대표적으로 암으로 통칭되는 질환에 대한 효과적이고 전통적인 치료 방법은 외과적으로 종양을 절제하여 제거하는 방법이 사용되었으나, 원발성 암이 타 기관으로 전이가 되는 경우는 외과적 수술이 불가하여 항암 약물 치료 요법이 사용되었다. 약물 치료로 사용되는 항암제는 주로 단분자 물질을 유기적 또는 무기적 방법으로 합성하여 사용하였는데, 이는 암 질환이 주로 신호 전달 체계에 포함된 인산 활성 인자 단백질의 과발현 등에 의하여 신호 체계를 교란 시키는 단백질에 효과적으로 결합하여 단백질의 활성을 억제하는 용도로 개발 되어 사용 되었다. 이러한 방식의 전통적 약물 치료법은 많은 부작용을 수반하는데, 그 중 한 가지는 약물로 사용되는 물질이 인위적으로 합성된 생체 외부 유래 물질이라는 것과 항암 물질의 작용점이 이미 과다 발현된 단백질을 목적으로 한다는 점이다.
상기 전통적인 약물 치료 방법을 대체하기 위한 약물 치료제의 개발이 여러 방면으로 진행 되었는데, 그 중 하나가 작은 간섭 RNA (small interfering RNA, 이하 siRNA 으로 표기) 의 이용이다(Iorns, E., Lord, C.J., Turner, N. & Ashworth, A. Utilizing RNA interference to enhance cancer drug discovery. Nat Rev Drug Discov 6, 556-68. 2007.). siRNA는 16에서 27사이의 뉴클레오티드로 구성된 단일 가닥 RNA 로서, 세포 내에서 리스크(RNA Induced Silencing Complex, RISC)라 알려진 리보핵산단백질 결합체 (ribonucleoprotein)의 구성 성분으로서 활동을 한다(Tomari, Y. & Zamore, P.D. Perspective: machines for RNAi. Genes Dev 19, 517-29, 2005, Chu, C.Y. & Rana, T.M. Potent RNAi by short RNA triggers. Rna 14, 1714-9, 2008, Mittal, V. Improving the efficiency of RNA interference in mammals. Nat Rev Genet 5, 355-65, 2004, Reynolds, A. et al. Rational siRNA design for RNA interference. Nat Biotechnol 22, 326-30. 2004). RISC는 RNA 효소 가위로서 기능을 하는데, 메신저 RNA (messenger RNA, 이하 mRNA 로 표기)를 절단하여 mRNA로부터 단백질이 생성되는 것을 저해한다. RISC에 포함된 siRNA는 siRNA 서열과 상보적인 서열을 갖는 mRNA와 결합하여 이중가닥 RNA를 형성하고, RISC는 RNA 효소 가위로 작용하여 목표가 되는 mRNA를 절단하여 mRNA가 더 이상 단백질을 반복 생성하는 형판 (template)으로서의 기능을 수행할 수 없도록 한다.
이처럼 siRNA 기반의 항암 치료제는 단백질 생성 단계 이전의 mRNA를 차단한다는 점, 그리고 RNA 와 세포 내재적인 RISC 시스템을 활용한다는 점에 있어서 상기 단분자 물질의 항암제보다 진보한 기술로 평가되나, siRNA 기반의 기술로도 해결하지 못하는 부작용이 있는데, 이는 비표적 효과 (off-target effect)로 불리는 현상이다(Jackson, A.L. et al. Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. Rna 12, 1179-87, 2006., Jackson, A.L. et al. Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. Rna 12, 1197-205, 2006., Jackson, A.L. et al. Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21, 635-7, 2003., Nielsen, C.B. et al. Determinants of targeting by endogenous and exogenous microRNAs and siRNAs. Rna 13, 1894-910, 2007., Peek, A.S. & Behlke, M.A. Design of active small interfering RNAs. Curr Opin Mol Ther 9, 110-8, 2007.). 상기 기술한 바와 같이 siRNA 서열과 상보적으로 결합하는 mRNA를 분해하는데, siRNA 서열 전체와 상보적이지 않고 일부분만 상보적인 mRNA와도 결합하여 분해를 유발하는데 이를 표적이 아닌 mRNA의 분해를 유발한다 하여 비표적 효과라 불린다.
상기 기술된 siRNA 기반의 항암 치료제의 기술적 난점을 극복하기 위하여 마이크로 RNA (microRNA, 이하 miRNA로 표기)를 치료제로 사용하려는 연구가 진행 중이다(Agostini, M. & Knight, R.A. miR-34: from bench to bedside. Oncotarget 5, 872-81, 2014., van Rooij, E., Purcell, A.L. & Levin, A.A. Developing MicroRNA Therapeutics. Circulation Research 110, 496-507, 2012., Burnett, J.C. & Rossi, J.J. RNA-based therapeutics: current progress and future prospects. Chem Biol 19, 60-71, 2012., Dangwal, S. & Thum, T. microRNA therapeutics in cardiovascular disease models. Annu Rev Pharmacol Toxicol 54, 185-203, 2014.). miRNA는 16에서 27사이의 뉴클레오티드로 구성된 RNA로서 단백질로 번역되는 메신저 RNA(mRNA)에 대비하여 단백질 비생성 RNA(protein non-coding RNA)로 분류된다(Carthew, R.W. & Sontheimer, E.J. Origins and Mechanisms of miRNAs and siRNAs. Cell 136, 642-55, 2009., MacFarlane, L.-A. & Murphy, P.R. MicroRNA: Biogenesis, Function and Role in Cancer. Current Genomics 11, 537-561, 2010., Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-33, 2009.). miRNA는 고등 동식물 세포의 유전체에 기록 되어 있으며 세포의 생성, 성장, 분화, 사멸을 포함한 세포의 대사 및 기능을 조절하는데 핵심적인 역할을 하는 것으로 알려져 있다. 현재까지 인간의 유전체에서는 2000 여종의 miRNA가 알려져 있으며 이 중 상당수의 miRNA의 기능은 아직 알려져 있지 않다.
miRNA는 유전체로부터 Pol II라 불리는 RNA 폴리머라제(polymerase)에 의해 RNA로 전사되는데, 초기 길이는 특정할 수 없이 다양하다(Carthew, R.W. & Sontheimer, E.J. Origins and Mechanisms of miRNAs and siRNAs. Cell 136, 642-55, 2009., Brodersen, P. & Voinnet, O. Revisiting the principles of microRNA target recognition and mode of action. Nat Rev Mol Cell Biol 10, 141-148, 2009.). 이는 miRNA가 유전체에 포함된 위치의 다양성에 기인하는데, mRNA의 단백질 생성 비관여 부분인 인트론 (intron)에 위치하여 mRNA 생성 동일 시점에 전사되는 경우 및 유전체상에서 유전자간 빈 공간 (inter-genic region)에 위치하여 독자적으로 전사되는 경우 등 다양한 방식으로 생성되기 때문이다(Malone, C.D. & Hannon, G.J. Small RNAs as guardians of the genome. Cell 136, 656-68, 2009.). 이와 같이 초기에 생성된 miRNA 모체를 일차 miR(primary microRNA)라 하는데, 일차 miR는 핵 속의 드로셔(Drosha)라 불리는 RNA 절단 효소(RNase) 등에 의하여 전구체 miR(precursor miRNA, pre-miR) 로 편집된다(Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-33, 2009.). Pre-miR는 RNA 헤어핀 구조(RNA hair-pin structure)를 이루며 대략 70-80 개의 뉴클레오티드로 구성된다. 세포 핵 내부의 Pre-miR는 exportin 단백질 등에 의해 핵에서 세포질로 이동되며, 세포질 내에서 다이서(Dicer)라 불리는 또 다른 RNA 절단 효소(RNase)에 의하여 이차 가공이 되어 16-27 개의 뉴클레오티드로 구성되는 이중 가닥의 성숙 miR(mature microRNA, 이하 다른 수식어 없이 miR 로 기술하는 경우는 성숙 miR를 의미함)를 생성한다. 이중 가닥 miR 중 한 가닥의 RNA 가 선택적으로 선정되어 상기 리보핵산단백질 결합체(ribonucleoprotein comple)인 RISC와 결합하여 활성을 가지게 되고, miR의 서열을 이용하여 목표 mRNA와 결합한다.
일반적으로 mRNA는 단백질 생성 관여 여부를 기준으로 크게 세 부분으로 나눌 수 있는데, 단백질 번역 정보를 담고 있는 코딩 부분(coding region)과 코딩 부분의 각각 5' 과 3' 부분으로서 단백질 번역 정보를 가지지 않는 5'-UTR(Un-Translated Region)과 3'-UTR로 구분할 수 있다. mRNA와의 상보적 서열을 이용, 목표 mRNA의 분해를 유발하는 siRNA는 mRNA 의 5'-, 3'-UTR 및 코딩 부분에 상관 없이 작용을 하는 반면, miR는 주로 3'-UTR과 결합을 한다((Carthew, R.W. & Sontheimer, E.J. Origins and Mechanisms of miRNAs and siRNAs. Cell 136, 642-55, 2009., Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-33, 2009.).
mRNA와의 결합 위치 차이와 더불어 siRNA와 다른 miRNA의 독특한 특징은 siRNA는 siRNA 전체 서열과 상보적인 서열을 포함한 mRNA와 주로 결합하는 반면, miRNA는 miRNA의 5' 끝으로부터 2-8 뉴클레오티드 자리에 위치한, 한정된 크기의 씨앗부분(seed region)서열이 주로 목표 mRNA 인식에 사용되는 점이 다르며, 따라서 전체 miRNA의 서열이 목표 유전자와 완벽한 상보적인 서열을 가지지 않고 일정 부분 비상보적 서열이 포함되어도 miRNA 활성에 영향을 주지 않는다(Bartel, D.P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215-33, 2009.). 씨앗 부분의 서열 크기가 6-8 뉴클레오티드인 만큼 이와 상보적인 서열을 3' UTR에 가지는 mRNA 종류는 다양하며, 이러한 이유로 한 종의 miRNA로 여러 종의 mRNA를 동시에 제어할 수 있다. 이러한 miRNA의 성질은 miRNA가 세포의 분열, 성장, 분화, 사멸에 이르는 많은 부분의 세포 생리학적 측면의 제어에 관여하는 효율적인 조절인자(regulator)로서의 기능을 부과한다. 또한, 조절인자로서의 miRNA 의 기능은 효과적인 항암 효과를 구현하는데 장점으로서 작용하는데, siRNA 의 경우 단일 유전자 발현의 억제를 목표로 하는데 반하여, miRNA 는 암 유발 유전자 다수의 발현을 동시에 저해할 수 있기 때문이다.
많은 수의 mRNA가 3' UTR에 한 종 이상의 miRNA가 결합할 가능성이 있는 부분을 포함하고 있으며, 한 생물정보학적인 계산에 따르면 전체 mRNA의 대략 30%가 miRNA에 의해 단백질 생성이 조절되고 있는 것으로 알려져 있다.
miRNA의 이러한 신호 전달 체계 내의 주요 조절인자로 작용하는 사실은 암을 포함한 주요 질환에서도 중요한 역할을 수행한다는 점에서 알 수 있다(MacFarlane, L.-A. & Murphy, P.R. MicroRNA: Biogenesis, Function and Role in Cancer. Current Genomics 11, 537-561. 2010., Malone, C.D. & Hannon, G.J. Small RNAs as guardians of the genome. Cell 136, 656-68. 2009., Nicoloso, M.S., Spizzo, R., Shimizu, M., Rossi, S. & Calin, G.A. MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer 9, 293-302. 2009., Landi, D., Gemignani, F. & Landi, S. Role of variations within microRNA-binding sites in cancer. Mutagenesis 27, 205-10. 2012.). 실제로 여러 연구를 통하여 암 세포에서의 miRNA들의 발현 양식은 정상 세포에서의 발현 양식과 큰 차이를 보이는 것이 드러났다. 뿐만 아니라 암이 발생한 원발 장기에 따라서도 miRNA 발현 양식이 큰 차이가 있는데 폐암, 간암, 피부암, 혈액암 등 다양한 암들이 원발 장기에 따른 독특한 miRNA 발현 양식을 보이고, 이를 통하여 miRNA가 암 생물학에 있어 주요한 역할을 한다는 것이 알려져 있다. 특히, 암 종에서 발현되는 miRNA들이 그들의 정상 세포에서의 발현양에 대비하여 일반적으로 낮은 것이 알려져 있다.
상기 암에 있어서의 miRNA의 깊은 연관성을 바탕으로 miRNA를 항암 치료제로 이용하려는 시도가 최근에 시작되었으며, 그 일례로 miR-34a라 명명된 miRNA의 암 세포 증식 억제 및 사멸 유도 능력을 검증하기 위한 임상 실험 중에 있다(Wiggins, J.F. et al. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res 70, 5923-30. 2010., Bader, A.G. et al. miR-34 Regulated Genes and Pathways as Targets for Therapeutic Intervention. Google Patents, 2009., Hermeking, H. The miR-34 family in cancer and apoptosis. Cell Death Differ 17, 193-9. 2010., Chang, T.C. et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26, 745-52. 2007.).
이에 본 발명자들은 임상 실험 중인 miR-34a의 암 세포 증식 억제 및 암 세포 사멸 유도 능력 보다 효능이 뛰어난 miRNA를 발굴하고자 노력한 결과, 항암 효능이 뛰어난 miR-3670, miR-4477a, miR-8078 를 발굴하고, 이들 miRNA 들이 암 유발 유전자로 알려진 다수의 유전자 발현을 효과적 차단함으로써 항암 효과를 달성하는 것을 확인함으로써 본 발명을 완성하였다.
본 발명의 목적은 암 세포 증식 억제 및 암 세포 사멸 유도 능력이 뛰어난 miRNA 를 발굴하고 이를 유효 성분으로 포함하는 암 치료용 약학 조성물을 제공하는 것이다..
상기 목적을 달성하기 위하여, 본 발명은 miR-3670, miR-4477a, miR-8078 로 구성된 군에서 선택되는 하나 이상의 miRNA를 유효 성분으로 포함하는 암 치료용 약학 조성물을 제공한다.
본 발명에 따른 암 치료용 약학 조성물은, miR-3670, miR-4477a, miR-8078, 로 구성된 군에서 선택되는 하나 이상의 miRNA를 유효 성분으로 포함하여, 기존의 항암제로서의 적합성을 측정하기 위하여 임상 실험 진행 중인 miR-34a 및 기타 다른 miRNA를 유효 성분으로 하는 암 치료용 약학 조성물 대비 개선된 항암 효과를 보이는 바 항암 치료 조성물로서 널리 활용될 수 있다.
도 1은 스크리닝 라이브러리 제작에 포함된 miRNA의 활성 여부를 측정하기 위하여 전체 스크리닝 라이브러리에서 대표적으로 miR-34a, miR-100 및 miR-125b를 선정하고 이들에 의해 발현이 저해된다고 알려진 각각의 mRNA 3'UTR을 루시퍼아제 (luciferase) 발현 벡터의 3'UTR 에 삽입하여 miR-34a, miR-100 및 miR-125b에 의한 단백질 발현 저해능을 확인한 것이다.
도 2는 1700 여종의 miRNA로 구성된 스크리닝 라이브러리를 NCI-H460 폐암 세포주에 처리하여 세포 성장을 레사주린(Resazurin) 시약을 사용하여 정량하고, 이를 상대적인 성장값으로 환산하여 나타낸 것이다.
도 3은 NCI-H460 세포주에서 우수한 효능을 보인 50 여종의 miRNA를 선별하고 이를 사용하여 상대적 암 세포 성장 저해 능력을 WST-1 시약으로 측정하여 나타낸 것이다.
도 4는 폐암 세포주에서의 세포 사멸 효과를 측정하기 위하여 miR-34a, miR-3670, miR-8078, miR-4477a 를 트랜스펙션 방식으로 세포내로 주입한 후 세포의 사멸 정도를 FITC 염료로 표지된 아넥신 V 로 염색하여 유세포분석기로 분석한 결과이다.
도 5는 폐암 세포주에 각 miRNA 를 트랜스펙션 방식으로 주입하고 소프트 아가 위에서 2 주간 배양하여 miRNA 의 영향에 따른 폐암 세포주의 군집 형성 능력을 측정한 것이다.
도 6은 miRNA 타겟 예측 소프트웨어인 타겟스캔을 사용하여 타겟 후보군을 선정하고, 이들을 타겟으로 하는 siRNA 를 사용하여 세포 내의 함량을 저해시킬 경우의 세포 사멸 능력을 Z-score 로 표시한 것이다.
도 7은 도 6에서 확인된 유전자들의 발현량이 miRNA 에 의하여 저해되는 정도를 qPCR 분석으로 나타낸 것이다.
도 8은 도 6에서 확인된 유전자들의 3' UTR 을 루시퍼아제의 3' UTR 에 클로닝하여 miRNA 에 의한 루시퍼아제 단백질의 발현 저해 정도를 표시한 것이다.
다른 식으로 정의되지 않는 한, 본 명세서에서 사용된 모든 기술적 및 과학적 용어들은 본 발명이 속하는 기술분야에서 숙련된 전문가에 의해서 통상적으로 이해되는 것과 동일한 의미를 갖는다. 일반적으로 본 명세서에서 사용된 명명법은 본 기술분야에서 잘 알려져 있고 통상적으로 사용되는 것이다.
본 발명에서는 항암 효과가 있다고 알려진 miR-34a보다 효능이 뛰어난 miRNA를 발굴하고, 이의 항암 효과를 확인하고자 하였다.
본 발명에서는 1700 여종의 miRNA 스크리닝 라이브러리를 합성하였고( 표 1), 이를 NCI-H460(폐암 세포주)에 처리하여, 암 세포 성장 억제능을 측정하여, miR-34a 보다 효능이 뛰어난, 하기의 염기 서열을 갖는 miR-3670, miR-4477a, miR-8078 를 발굴하고( 표 3), 이들의 항암 효능이 뛰어남을 확인하였다(도 4 내지 도 8).
따라서 본 발명은 miR-3670, miR-4477a, miR-8078로 구성된 군에서 선택되는 하나 이상의 miRNA를 유효 성분으로 포함하는 암 치료용 약학 조성물에 관한 것이다.
본 발명에 있어서, 상기 miR-3670 는 서열 번호 35와 서열 번호 36 또는 서열 번호 67의 염기 서열로 이루어진 이중 가닥 RNA 을 유효 성분으로 포함되는 것을 특징으로 할 수 있다.
본 발명에 있어서, 상기 miR-4477a 는 서열 번호 43과 서열 번호 44 또는 서열 번호 68 의 염기 서열로 이루어진 이중 가닥 RNA 을 유효 성분으로 포함되는 것을 특징으로 할 수 있다.
본 발명에 있어서, 상기 miR-8078 는 서열 번호 65와 서열 번호 66 또는 서열 번호 69 의 염기 서열로 이루어진 이중 가닥 RNA 을 유효 성분으로 포함되는 것을 특징으로 할 수 있다.
즉, 본 발명의 miR-3670 주형 가닥은 서열번호 35로 표시되는 것을 특징으로 할 수 있다.
5'- AGAGCUCACAGCUGUCCUUCUCUA - 3'(MIMAT0018093. 서열번호 35)
생체내에서 궁극적으로 활성을 보이는 miRNA 는 단일 가닥이지만, RISC 에 결합하기 위하여서는 유사한 염기 크기를 갖는 염기 서열과 함께 이중 가닥 형태로 세포내에 공급되어야 한다. 이때, 상기 서열과 결합하는 반대 서열 (antisense) 는 활성 서열과 상보적인 서열을 가진다. 상보적인 서열은 완벽 상보 서열 (perfect complementary sequence) 를 가지거나, 또는 생체 내재적인 서열 (endogenous sequence ) 을 사용할 수 있다. 이중 가닥으로 구성된 각 서열 모두, 혹은 한 쪽 가닥의 3' 에 위치한 염기는 상대 서열과의 염기 결합을 가지지 않을 수 있는데, 이를 3' 오버행 (overhang) 이라 하며 이를 포함할 수 있다.
즉, miR-3670 의 완벽 상보 서열 (perfect complementary sequence)은 서열번호 36으로 표시되는 것을 특징으로 할 수 있다.
5' - GAGAAGGACAGCUGUGAGCUCUUU - 3' (서열번호 36)
또한, miR-3670 의 내재적 상보 서열 (endogenous complementary sequence)은 서열번호 67로 표시되는 것을 특징으로 할 수 있다.
5' - GACUGGUAUAGCUGCUUUUGGAGCCUCA - 3' (서열번호 67)
상기 배경 기술에서 기술한 바와 같이 miRNA 활성 서열의 두 번째 염기로부터 8-9 번째 염기까지 해당하는 씨앗 서열 (seed region) 이 활성의 주요한 인자인데, 이중 가닥 RNA 를 제조할 때 이를 포함하는 긴 이중 가닥을 제조하여 사용할 수도 있다.
miR-3670 과 마찬가지로 miR-4477a 및 miR-8078 의 활성 서열 및 이들과 이중 가닥을 이루기 위한 상보 서열은 아래에 기재된 바와 같이 표시되는 것을 특징으로 할 수 있다. 이들 이중 가닥도 전술한 바와 같이 3' 오버행을 포함하여 이중 가닥을 구성할 수 있으며, 또한 씨앗 지역 (seed region) 을 포함한 긴 서열의 이중 가닥을 구성하여 사용할 수 있다.
miR-4477a
5' - CUAUUAAGGACAUUUGUGAUUC -3' (MIMAT0019004 서열번호 43)
miR-4477a 의 완벽 상보 서열 (perfect complementary sequence)
5'- AUCACAAAUGUCCUUAAUAGUU -3' (서열번호 44)
miR-4477a 의 내재 상보 서열 (endogenous complementary sequence)
5'- AUCACAAAUGUCCUUAAUGGCA -3' (서열번호 68)
miR-8078
5'- GGUCUAGGCCCGGUGAGAGACUC (MIMAT0031005, 서열번호 65)
miR-8078 의 완벽 상보 서열 (perfect complementary sequence)
5'- GUCUCUCACCGGGCCUAGACCUU (서열번호 66)
miR-8078 의 내재 상보 서열 (endogenous complementary sequence)
5'- CUCCACCGGGCUGACCGGCCUG -3' (서열번호 69)
본 발명에서 라이브러리 스크린을 통하여 발굴된 상기 miRNA 는 암의 유발, 생성 및 성장에 주요한 역할을 하는 것으로 통상적으로 알려진 유전자를 제어함으로써 항암 효능을 발생시키는 것을 확인하였다. 한 종의 miRNA 가 다수의 mRNA 발현을 동시에 제어 할 수 있는 것이 miRNA 의 특징인데, 이러한 성질은 본 발명에서도 확인 되었으며, 올리고 기반의 항암 신약 개발에 유용한 성질이다.
본 발명의 miR-3670 은 CBX4, NRAS, CASR, TXLNA, SNIP1, HNF1A, FZD4, TRIB1, ADMA19, CKAP5 의 발현을 동시에 억제하고, miR-8078 은 GREB1, HECTD3, RIPK4 의 발현을 억제하며, miR-4477a 는 STIL, KIF11, AKAP11, FAM120A 의 발현을 동시에 억제함을 확인하였다(도 6).
본 발명의 miRNA가 억제하는 타겟 유전자들은 하기와 같은 기능을 하는 것으로알려져 있다.
CBX4 (polycomb chromobox 4) 는 종양의 혈관 생성 및 종양의 전이 촉진에 관여하며 NRAS 는 종양의 성장 및 세포 분열에 주요한 역할을 수행한다고 알려져 있다(Orouji, E. et al. MAP Kinase pathway gene copy alterations in NRAS/BRAF wild-type advanced melanoma. Int J Cancer (2015); Zheng, C. et al. MicroRNA-195 functions as a tumor suppressor by inhibiting CBX4 in hepatocellular carcinoma. Oncol Rep 33, 1115-22 (2015); Jiao, H.K. et al. Prognostic significance of Cbx4 expression and its beneficial effect for transarterial chemoembolization in hepatocellular carcinoma. Cell Death Dis 6, e1689 (2015); Ohashi, K. et al. Characteristics of lung cancers harboring NRAS mutations. Clin Cancer Res 19, 2584-91 (2013)).
CASR 은 종양에서 과다 발현되는 것이 발견되고 종양의 전이에 필요하며, TXLNA 는 종양의 성장 및 전이에 관련된 것으로 알려져 있는데 발현률이 높은 환자군의 생존율이 낮다는 임상 결과가 발표되었다(Mashidori, T., Shirataki, H., Kamai, T., Nakamura, F. & Yoshida, K. Increased alpha-taxilin protein expression is associated with the metastatic and invasive potential of renal cell cancer. Biomed Res 32, 103-10 (2011); Tennakoon, S., Aggarwal, A. & Kallay, E. The calcium-sensing receptor and the hallmarks of cancer. Biochim Biophys Acta (2015); Ohtomo, N. et al. Expression of alpha-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor. Int J Oncol 37, 1417-23 (2010)).
전사 공동 활성 인자 (transcriptional coactivator) 로 알려진 SNIP1 은 세포의 성장 및 분열에 필수적인 cyclin D1 의 발현을 촉진시키는데 SNIP1 의 발현량이 높은 환자군의 항암 예후가 좋지 않다는 것이 알려져 있다. 또한, 세포 증식의 주요 조절자로서의 역할을 하는 c-Myc 과 결합하여 종양 성장을 촉진하는 역할을 한다고 알려져 있다(Li, Q. et al. SNIP1: a new activator of HSE signaling pathway. Mol Cell Biochem 362, 1-6 (2012); Fujii, M. et al. SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes. Mol Cell 24, 771-83 (2006); Roche, K.C., Rocha, S., Bracken, C.P. & Perkins, N.D. Regulation of ATR-dependent pathways by the FHA domain containing protein SNIP1. Oncogene 26, 4523-30 (2007); Jeon, H.S. et al. High expression of SNIP1 correlates with poor prognosis in non-small cell lung cancer and SNIP1 interferes with the recruitment of HDAC1 to RB in vitro. Lung Cancer 82, 24-30 (2013); Liang, X. et al. Hypoxia-inducible factor-1 alpha, in association with TWIST2 and SNIP1, is a critical prognostic factor in patients with tongue squamous cell carcinoma. Oral Oncol 47, 92-7 (2011))
HNF1A 와 FZD4 는 종양의 성장 및 생존에 깊이 관여하는 Wnt 신호 전달 체계의 구성 인자이며 Wnt 신호 전달 체계는 종양 생물학에서 집중적으로 연구되어 그 중요성이 널리 알려져 있다. TRIB1 은 종양 세포의 성장, 전이 및 세포의 자살 억제 역할이 알려져 있으며 이는 종양 성장의 주된 신호 전달 체계의 하나인 MAPK 신호 전달 체계를 조절하는 인자로 알려져 있다(Pecina-Slaus, N. et al. Wnt signaling transcription factors TCF-1 and LEF-1 are upregulated in malignant astrocytic brain tumors. Histol Histopathol 29, 1557-64 (2014); Ueno, K. et al. Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4. Mol Cancer Ther 11, 244-53 (2012); Lin, Z.Y. et al. MicroRNA-224 inhibits progression of human prostate cancer by downregulating TRIB1. Int J Cancer 135, 541-50 (2014); Soubeyrand, S., Naing, T., Martinuk, A. & McPherson, R. ERK1/2 regulates hepatocyte Trib1 in response to mitochondrial dysfunction. Biochim Biophys Acta 1833, 3405-14 (2013)).
ADAM19 은 세포막에 분포하여 있는 단백질로서 세포-세포간 접촉과 세포-세포외 매트릭스와의 접촉을 포함한 생물학적 다양한 역할을 수행하는 것으로 알려져 있는데 종양 생물학에서는 종양의 성장 및 전이와 깊은 연관이 있는 것으로 알려져 있다. 유전자 기능적 스크린을 통하여 종양의 생존에 중요한 역할을 수행하는 것으로 알려진 CKAP5 유전자도 상기 miRNA 에 의하여 제어되는 것으로 본 발명을 통하여 밝혀졌으며, GREB1 은 호르몬에 반응하는 조직 또는 종양의 신호 전달 체계와 관련이 있는 유전자로서 다양한 종류의 종양에서 과다 발현하여 세포의 성장을 촉진시킨다고 알려져 있다(Zhang, Q. et al. Role of microRNA-30c targeting ADAM19 in colorectal cancer. PLoS One 10, e0120698 (2015); Shan, N., Shen, L., Wang, J., He, D. & Duan, C. MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targetin;g ADAM19. Biochem Biophys Res Commun 456, 385-91 (2015); Martens-de Kemp, S.R. et al. Functional genetic screens identify genes essential for tumor cell survival in head and neck and lung cancer. Clin Cancer Res 19, 1994-2003 (2013); Rae, J.M. et al. GREB1 is a novel androgen-regulated gene required for prostate cancer growth. Prostate 66, 886-94 (2006); Zhang, L. et al. Development of transcriptomic biomarker signature in human saliva to detect lung cancer. Cell Mol Life Sci 69, 3341-50 (2012); Laviolette, L.A., Hodgkinson, K.M., Minhas, N., Perez-Iratxeta, C. & Vanderhyden, B.C. 17beta-estradiol upregulates GREB1 and accelerates ovarian tumor progression in vivo. Int J Cancer 135, 1072-84 (2014)).
HECTD3 는 E3 유비퀴틴 리가제 (E3 ubiquitin ligase) 로서 세포의 자살을 촉발하는 캐스파제-8 (caspase-8) 에 폴리유비퀴틴을 부착하여 캐스파제-8 의 분해를 유도함으로써 종양의 사멸을 억제하는 한편, MALT1 단백질을 안정화시켜 시스플라틴 (cisplatin) 항암제에 대한 약물 저항성을 증대 시키는 것으로 알려져 있다. RIPK4 는 수용체 반응 단백질 키나제 4 (receptor-interactin protein kinase 4) 로서 세포 성장 신호 인자인 베타-카테닌 (β-catennin) 의 축적을 유발함과 동시에 Wnt 신호 전달 체계를 활성화하는 것으로 보고되어 있다. RIPK4 의 인위적 제거를 통하여 종양 동물 모델에서의 종양의 성장을 억제할 수 있음이 밝혀져 있다(Li, Y. et al. The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyubiquitination of caspase-8. Cell Death Dis 4, e935 (2013); Li, Y. et al. The HECTD3 E3 ubiquitin ligase suppresses cisplatin-induced apoptosis via stabilizing MALT1. Neoplasia 15, 39-48 (2013); Huang, X. et al. Phosphorylation of Dishevelled by protein kinase RIPK4 regulates Wnt signaling. Science 339, 1441-5 (2013)).
세포 주기 순환 중 G2 상 (phase) 에서 M 상(phase) 로의 전이 과정 중 필수적인 요소로서의 STIL 유전자는 다양한 종류의 암 종에서 발현율이 높은 것으로 관측되며, 종양 증식과 생존에 필요한 것으로 알려져 있다. KIF11 또한 종양 세포의 성장 및 전이에 필요한 요소 중 하나로 보고 되어 있으며 KIF11 의 활동을 저해함으로써 종양의 성장을 억제할 수 있다고 알려져 있다(Erez, A. et al. Sil overexpression in lung cancer characterizes tumors with increased mitotic activity. Oncogene 23, 5371-7 (2004); Erez, A. et al. The SIL gene is essential for mitotic entry and survival of cancer cells. Cancer Res 67, 4022-7 (2007); Tang, Y., Orth, J.D., Xie, T. & Mitchison, T.J. Rapid induction of apoptosis during Kinesin-5 inhibitor-induced mitotic arrest in HL60 cells. Cancer Lett 310, 15-24 (2011); Venere, M. et al. The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma. Sci Transl Med 7, 304ra143 (2015)).
단백질 키나제 A (PKA) 와 결합하여 PKA 의 활성을 증가시키는 AKAP11 는 GSK-3beta 와도 동시에 결합하여 PKA 에 의한 GSK-3beta 의 인산화 작용을 촉진 시킨다. 인산화 GSK-3beta 는 활성을 잃게 되는데, 이는 세포에서 성장을 촉진시키는 신호로 인식되어 종양의 성장을 유발하는 주요 기전 중의 하나이다. 종양 세포들은 산성 조건, 산소 결핍 조건 등의 다양한 스트레스 조건에 노출되는데, 이러한 가호한 조건 속에서도 종양 세포의 사멸을 억제하는 기전을 유지하고 있다. 그 하나로서 RNA 결합 단백질인 FAM120A 는 Src 등의 키나제 (Kinase) 를 활성화시켜 세포의 사멸 억제 및 약물에 대한 저항성을 증가시키는 것으로 알려져 있다(Logue, J.S. et al. AKAP220 protein organizes signaling elements that impact cell migration. J Biol Chem 286, 39269-81 (2011); Whiting, J.L. et al. Protein Kinase A Opposes the Phosphorylation-dependent Recruitment of Glycogen Synthase Kinase 3beta to A-kinase Anchoring Protein 220. J Biol Chem 290, 19445-57 (2015); Tanji, C. et al. A-kinase anchoring protein AKAP220 binds to glycogen synthase kinase-3beta (GSK-3beta ) and mediates protein kinase A-dependent inhibition of GSK-3beta. J Biol Chem 277, 36955-61 (2002); Tanaka, M. et al. A novel RNA-binding protein, Ossa/C9orf10, regulates activity of Src kinases to protect cells from oxidative stress-induced apoptosis. Mol Cell Biol 29, 402-13 (2009); Bartolome, R.A. et al. IL13 Receptor alpha2 Signaling Requires a Scaffold Protein, FAM120A, to Activate the FAK and PI3K Pathways in Colon Cancer Metastasis. Cancer Res 75, 2434-44 (2015)).
본 발명에서는 상기 유전자들을 siRNA 를 사용하여 세포내 함량을 저하시키면 miR-3670, miR4477a, miR-8078 을 사용하는 경우와 마찬가지로 세포의 성장이 저하되는 것을 확인하였으며(도 6), miR-3670, miR-4477a, miR-8078 을 폐암 세포내로 전달하는 경우, 상기 유전자들의 mRNA 발현이 저하되는 것을 모두 qPCR 결과로서 확인하였다(도 7). 또한, 상기 유전자들이 miR-3670, miR-4477a, miR-8078 의 직접적인 타겟임을 루시퍼아제 결과로서 확인하였다(도 8). 이러한 사실은 miR-3670, miR-4477a, miR-8078 이 종양 세포의 성장 및 생존에 중요한 여러 유전자를 직접적인 방식으로 발현을 동시에 억제함으로써 종양 세포의 사멸을 유도한다는 것을 의미한다.
본 발명에 있어서, 상기 암은 폐암, 간암, 위암, 대장암, 췌장암, 담낭 및 담도암, 유방암, 백혈병, 식도암, 비호치킨 림프종, 갑상선암, 자궁경부암, 피부암의 원발성 암과 이로부터 기타 장기로 전이되어 유발되는 전이암 및 비정상적인 과다 세포 분열을 촉진하여 생성되는 종양성 세포 질환으로 구성되는 군으로부터 선택된 1종 이상의 암인 것을 특징으로 하나 이에 한정되지 않는다.
본 발명에서 제공하는 암 치료용 약학 조성물의 유효성분으로서 사용 가능한 miRNA 서열은 인간 유전체 유래의 서열이나, miRNA의 유래 유전체를 인간 유전체로 한정하지 않고 다른 동물 유래 유전체부터 구해진 miRNA 서열 역시 사용할 수 있다.
본 발명에서 miRNA는 miRNA의 생물학적 등가 효능을 발생시키는 다양한 miRNA 유도체(miRNA mimic)의 형태로 사용할 수 있는데, 동일한 씨앗 부분 (seed region)을 포함하는 miRNA 서열을 포함하는 변형된 miRNA를 사용할 수 있다. 이 때 서열 1 또는 서열 2의 길이를 줄일 수 있는데, 길이가 15개 의 뉴클레오티드로 구성된 짧은 유도체 사용도 가능하다.
본 발명에서 상기 miRNA에 대한 miRNA 유도체로서는 RNA 인산 뼈대 구조 (phosphate backbone structure)를 황 등의 다른 원소로 치환한 형태인 포스포로사이오에이트 (phosphorothiolate) 구조를 부분적으로 포함할 수 있으며, RNA 대신 DNA, PNA(petide nucleic acids) 및 LNA(locked nucleic acid) 분자로의 전체 또는 부분적으로 치환한 형태로 사용 가능하고, 또한, RNA 당의 2'수산화기를 다양한 기능성 구조로 치환한 형태로 사용이 가능한데 , 이는 메틸화, 메톡시화, 플르오르화 등을 포함하나 이러한 변형에 한정되는 것은 아니다.
본 발명에서 miRNA는 성숙 miRNA(mature miRNA)와 이로부터 유도된 상기 miRNA 유도체의 이중 가닥 RNA에 한정하는 것이 아니고, miRNA 전구체의 형태로 사용될 수 있으며, miRNA 전구체 또한 상기 기술된 RNA 인산 뼈대 구조, RNA 핵산의 DNA, PNA 및 LNA 등으로의 부분 또는 전체 치환, RNA 당 분자의 2'수산화기의 변형이 가능하다.
본 발명에서 miRNA는 miRNA 전구체 또는 일차 miRNA (pri-miRNA) 형태로 사용 가능한데 이를 화학적인 방법으로 합성하거나 또는 플라스미드 (plasmid)의 형태로 세포로 전달하여 발현하는 것이 가능하다.
본 발명에 있어서, miRNA를 배양 접시에서 배양한 세포로 전달하는 방법은 양이온성 지질과의 혼합물 사용하는 방법, 전기적인 자극으로 전달하는 방법 및 바이러스를 이용하는 방법등을 사용할 수 있으나 이러한 방법에 제한을 두는 것은 아니다.
본 발명의 상기 miRNA를 유효성분으로 포함하는 암 치료용 약학 조성물은 약학적으로 허용 가능한 담체를 추가로 포함할 수 있으며, 함체와 함께 제제화 될 수 있다.
본 발명에서 용어, "약학적으로 허용 가능한 담체"란 생물체를 자극하지 않고 투여 화합물의 생물학적 활성 및 특성을 저해하지 않는 담체 또는 희석제를 말한다. 액상 용액으로 제제화되는 조성물에 있어서 허용되는 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.
본 발명의 상기 miRNA 및 약학적으로 허용 가능한 담체를 포함하는 암 예방 또는 치료용 조성물은 이를 유효성분으로 포함하는 어떠한 제형으로도 적용가능하며, 경구용 또는 비경구용 제형으로 제조할 수 있다. 본 발명의 약학적 제형은 구강(oral), 직장(rectal), 비강(nasal), 국소(topical; 볼 및 혀 밑을 포함), 피하, 질(vaginal) 또는 비경구(parenteral; 근육내, 피하 및 정맥내를 포함) 투여에 적당한 것 또는 흡입 (inhalation) 또는 주입(insufflation)에 의한 투여에 적당한 형태를 포함한다.
본 발명의 조성물을 유효성분으로 포함하는 경구 투여용 제형으로는, 예를 들어 정제, 트로키제, 로렌지, 수용성 또는 유성현탁액, 조제분말 또는 과립, 에멀젼, 하드 또는 소프트 캡슐, 시럽 또는 엘릭시르제로 제제화할 수 있다. 정제 및 캡슐 등의 제형으로 제제화하기 위해, 락토오스, 사카로오스, 솔비톨, 만니톨, 전분, 아밀로펙틴, 셀룰로오스 또는 젤라틴과 같은 결합제, 디칼슘 포스페이트와 같은 부형제, 옥수수 전분 또는 고구마 전분과 같은 붕괴제, 스테아르산 마스네슘, 스테아르산 칼슘, 스테아릴푸마르산 나트륨 또는 폴리에틸렌글리콜 왁스와 같은 윤활유를 포함할 수 있으며, 캡슐제형의 경우 상기 언급한 물질 외에도 지방유와 같은 액체 담체를 더 함유할 수 있다.
본 발명의 조성물을 유효성분으로 포함하는 비경구 투여용 제형으로는, 피하주사, 정맥주사 또는 근육내 주사 등의 주사용 형태, 좌제 주입방식 또는 호흡기를 통하여 흡입이 가능하도록 하는 에어로졸제 등 스프레이용으로 제제화할 수 있다. 주사용 제형으로 제제화하기 위해서는 본 발명의 조성물을 안정제 또는 완충제와 함께 물에서 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알의 단위 투여용으로 제제화할 수 있다. 좌제로 주입하기 위해서는, 코코아버터 또는 다른 글리세라이드 등 통상의 좌약 베이스를 포함하는 좌약 또는 관장제와 같은 직장투여용 조성물로 제제화할 수 있다. 에어로졸제 등의 스프레이용으로 제형화하는 경우, 수분산된 농축물 또는 습윤 분말이 분산되도록 추진제 등이 첨가제와 함께 배합될 수 있다.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.
실시예 1: miRNA 스크리닝 라이브러리 제작
miRNA 데이터베이스인 miRBase (www.mirbase.org) 에서 제공하는 21 버전의 인간 miRNA 서열로서 줄기고리 구조 (stem-loop structure) 기준으로 1700 여종의 miRNA 스크리닝 라이브러리를 통상의 올리고 합성에 사용되는 고체 합성법으로 두 가닥 서열의 miRNA 합성하였다. 합성된 miRNA 각 가닥은 C18 수지를 사용하여 역상 분리 방식 (reverse phase separation) 으로 정제하였다. 합성된 모든 miRNA 가닥은 MALDI-TOF 방식의 질량 분석기를 사용하여 의도한 서열의 합성 여부를 판별 및 확인하였다. 이중 가닥의 miRNA를 제조하기 위하여 상응하는 상보 가닥을 염 존재하에서 95°C 2분간 가열 후 서서히 냉각하여 이중 가닥을 결합시켰다.
miRNA 서열
miRNA 서열 1 서열 2
hsa-let-7a-1 UGAGGUAGUAGGUUGUAUAGUU CUAUACAAUCUACUGUCUUUC
hsa-let-7a-2 UGAGGUAGUAGGUUGUAUAGUU CUGUACAGCCUCCUAGCUUUCC
hsa-let-7b CUAUACAACCUACUGCCUUCCC UGAGGUAGUAGGUUGUGUGGUU
hsa-let-7c UGAGGUAGUAGGUUGUAUGGUU CUGUACAACCUUCUAGCUUUCC
hsa-let-7d CUAUACGACCUGCUGCCUUUCU AGAGGUAGUAGGUUGCAUAGUU
hsa-let-7e CUAUACGGCCUCCUAGCUUUCC UGAGGUAGGAGGUUGUAUAGUU
hsa-let-7f-1 UGAGGUAGUAGAUUGUAUAGUU CUAUACAAUCUAUUGCCUUCCC
hsa-let-7f-2 UGAGGUAGUAGAUUGUAUAGUU CUAUACAGUCUACUGUCUUUCC
hsa-let-7g CUGUACAGGCCACUGCCUUGC UGAGGUAGUAGUUUGUACAGUU
hsa-let-7i UGAGGUAGUAGUUUGUGCUGUU CUGCGCAAGCUACUGCCUUGCU
hsa-miR-1 UGGAAUGUAAAGAAGUAUGUAU ACAUACUUCUUUAUAUGCCCAU
hsa-miR-100 CAAGCUUGUAUCUAUAGGUAUG AACCCGUAGAUCCGAACUUGUG
hsa-miR-101 UACAGUACUGUGAUAACUGAA CAGUUAUCACAGUGCUGAUGCU
hsa-miR-103a AGCAGCAUUGUACAGGGCUAUGA AGCUUCUUUACAGUGCUGCCUUG
hsa-miR-103b UCAUAGCCCUGUACAAUGCUGCU CAGCAUUGUACAGGGCUAUGAUU
hsa-miR-105 UCAAAUGCUCAGACUCCUGUGGU ACGGAUGUUUGAGCAUGUGCUA
hsa-miR-106a CUGCAAUGUAAGCACUUCUUAC AAAAGUGCUUACAGUGCAGGUAG
hsa-miR-106b UAAAGUGCUGACAGUGCAGAU CCGCACUGUGGGUACUUGCUGC
hsa-miR-107 AGCAGCAUUGUACAGGGCUAUCA AUAGCCCUGUACAAUGCUGCUUU
hsa-miR-10a CAAAUUCGUAUCUAGGGGAAUA UACCCUGUAGAUCCGAAUUUGUG
hsa-miR-10b ACAGAUUCGAUUCUAGGGGAAU UACCCUGUAGAACCGAAUUUGUG
hsa-miR-1178 UUGCUCACUGUUCUUCCCUAG CAGGGUCAGCUGAGCAUG
hsa-miR-1179 AAGCAUUCUUUCAUUGGUUGG AACCAAUGAAAGAAUGCUUUU
hsa-miR-1180 UUUCCGGCUCGCGUGGGUGUGU GGACCCACCCGGCCGGGAAUA
hsa-miR-1181 CCGUCGCCGCCACCCGAGCCG GCUCGGGUGGCGGCGACGGUU
hsa-miR-1182 GAGGGUCUUGGGAGGGAUGUGAC CACAUCCCUCCCAAGACCCUCUU
hsa-miR-1183 CACUGUAGGUGAUGGUGAGAGUGGGCA CCCACUCUCACCAUCACCUACAGUGUU
hsa-miR-1184 CCUGCAGCGACUUGAUGGCUUCC AAGCCAUCAAGUCGCUGCAGGUU
hsa-miR-1185-1 AGAGGAUACCCUUUGUAUGUU AUAUACAGGGGGAGACUCUUAU
hsa-miR-1185-2 AGAGGAUACCCUUUGUAUGUU AUAUACAGGGGGAGACUCUCAU
hsa-miR-1193 GGGAUGGUAGACCGGUGACGUGC ACGUCACCGGUCUACCAUCCCUU
hsa-miR-1197 UAGGACACAUGGUCUACUUCU AAGUAGACCAUGUGUCCUAUU
hsa-miR-1199 CCUGAGCCCGGGCCGCGCAG UGCGGCCGGUGCUCAACCUGC
hsa-miR-1200 CUCCUGAGCCAUUCUGAGCCUC GGCUCAGAAUGGCUCAGGAGUU
hsa-miR-1202 GUGCCAGCUGCAGUGGGGGAG CCCCCACUGCAGCUGGCACUU
hsa-miR-1203 CCCGGAGCCAGGAUGCAGCUC GCUGCAUCCUGGCUCCGGGUU
hsa-miR-1204 UCGUGGCCUGGUCUCCAUUAU AAUGGAGACCAGGCCACGAUU
hsa-miR-1205 UCUGCAGGGUUUGCUUUGAG CAAAGCAAACCCUGCAGAUU
hsa-miR-1206 UGUUCAUGUAGAUGUUUAAGC UUAAACAUCUACAUGAACAUU
hsa-miR-1207 UGGCAGGGAGGCUGGGAGGGG UCAGCUGGCCCUCAUUUC
hsa-miR-1208 UCACUGUUCAGACAGGCGGA CGCCUGUCUGAACAGUGAUU
hsa-miR-122 UGGAGUGUGACAAUGGUGUUUG AACGCCAUUAUCACACUAAAUA
hsa-miR-1224 CCCCACCUCCUCUCUCCUCAG GUGAGGACUCGGGAGGUGG
hsa-miR-1225 GUGGGUACGGCCCAGUGGGGGG UGAGCCCCUGUGCCGCCCCCAG
hsa-miR-1226 GUGAGGGCAUGCAGGCCUGGAUGGGG UCACCAGCCCUGUGUUCCCUAG
hsa-miR-1227 GUGGGGCCAGGCGGUGG CGUGCCACCCUUUUCCCCAG
hsa-miR-1228 GUGGGCGGGGGCAGGUGUGUG UCACACCUGCCUCGCCCCCC
hsa-miR-1229 GUGGGUAGGGUUUGGGGGAGAGCG CUCUCACCACUGCCCUCCCACAG
hsa-miR-1231 GUGUCUGGGCGGACAGCUGC AGCUGUCCGCCCAGACACUU
hsa-miR-1233 AGUGGGAGGCCAGGGCACGGCA UGAGCCCUGUCCUCCCGCAG
hsa-miR-1234 UCGGCCUGACCACCCACCCCAC GGGGUGGGUGGUCAGGCCGAUU
hsa-miR-1236 UGAGUGACAGGGGAAAUGGGGA CCUCUUCCCCUUGUCUCUCCAG
hsa-miR-1237 CGGGGGCGGGGCCGAAGCGCG UCCUUCUGCUCCGUCCCCCAG
hsa-miR-1238 CUUCCUCGUCUGUCUGCCCC GUGAGUGGGAGCCCCAGUGUGUG
hsa-miR-124 UAAGGCACGCGGUGAAUGCC CGUGUUCACAGCGGACCUUGAU
hsa-miR-1243 AACUGGAUCAAUUAUAGGAGUG CUCCUAUAAUUGAUCCAGUUUU
hsa-miR-1244 AAGUAGUUGGUUUGUAUGAGAUGGUU CCAUCUCAUACAAACCAACUACUUUU
hsa-miR-1245a AAGUGAUCUAAAGGCCUACAU GUAGGCCUUUAGAUCACUUUU
hsa-miR-1245b UCAGAUGAUCUAAAGGCCUAUA UAGGCCUUUAGAUCACUUAAA
hsa-miR-1246 AAUGGAUUUUUGGAGCAGG UGCUCCAAAAAUCCAUUUU
hsa-miR-1247 CCCCGGGAACGUCGAGACUGGAGC ACCCGUCCCGUUCGUCCCCGGA
hsa-miR-1248 ACCUUCUUGUAUAAGCACUGUGCUAAA UAGCACAGUGCUUAUACAAGAAGGUUU
hsa-miR-1249 ACGCCCUUCCCCCCCUUCUUCA AGGAGGGAGGAGAUGGGCCAAGUU
hsa-miR-1250 ACAUUUUCCAGCCCAUUCA ACGGUGCUGGAUGUGGCCUUU
hsa-miR-1251 CGCUUUGCUCAGCCAGUGUAG ACUCUAGCUGCCAAAGGCGCU
hsa-miR-1252 AGAAGGAAAUUGAAUUCAUUUA CAAAUGAGCUUAAUUUCCUUUU
hsa-miR-1253 AGAGAAGAAGAUCAGCCUGCA CAGGCUGAUCUUCUUCUCUUU
hsa-miR-1254 AGCCUGGAAGCUGGAGCCUGCAGU UGCAGGCUCCAGCUUCCAGGCUUU
hsa-miR-1255a AGGAUGAGCAAAGAAAGUAGAUU UCUACUUUCUUUGCUCAUCCUUU
hsa-miR-1255b AACCACUUUCUUUGCUCAUCCA CGGAUGAGCAAAGAAAGUGGUU
hsa-miR-1256 AGGCAUUGACUUCUCACUAGCU CUAGUGAGAAGUCAAUGCCUUU
hsa-miR-1257 AGUGAAUGAUGGGUUCUGACC UCAGAACCCAUCAUUCACUUU
hsa-miR-1258 AGUUAGGAUUAGGUCGUGGAA CCACGACCUAAUCCUAACUUU
hsa-miR-125a ACAGGUGAGGUUCUUGGGAGCC UCCCUGAGACCCUUUAACCUGUGA
hsa-miR-125b-1 UCCCUGAGACCCUAACUUGUGA ACGGGUUAGGCUCUUGGGAGCU
hsa-miR-125b-2 UCCCUGAGACCCUAACUUGUGA UCACAAGUCAGGCUCUUGGGAC
hsa-miR-126 UCGUACCGUGAGUAAUAAUGCG CAUUAUUACUUUUGGUACGCG
hsa-miR-1260a AUCCCACCUCUGCCACCA GUGGCAGAGGUGGGAUUU
hsa-miR-1260b AUCCCACCACUGCCACCAU GGUGGCAGUGGUGGGAUUU
hsa-miR-1261 AUGGAUAAGGCUUUGGCUU GCCAAAGCCUUAUCCAUUU
hsa-miR-1262 AUGGGUGAAUUUGUAGAAGGAU CCUUCUACAAAUUCACCCAUUU
hsa-miR-1263 AUGGUACCCUGGCAUACUGAGU UCAGUAUGCCAGGGUACCAUUU
hsa-miR-1264 CAAGUCUUAUUUGAGCACCUGUU CAGGUGCUCAAAUAAGACUUGUU
hsa-miR-1265 CAGGAUGUGGUCAAGUGUUGUU CAACACUUGACCACAUCCUGUU
hsa-miR-1266 CCUCAGGGCUGUAGAACAGGGCU CCCUGUUCUAUGCCCUGAGGGA
hsa-miR-1267 CCUGUUGAAGUGUAAUCCCCA GGGAUUACACUUCAACAGGUU
hsa-miR-1268a CGGGCGUGGUGGUGGGGG CCCACCACCACGCCCGUU
hsa-miR-1268b CGGGCGUGGUGGUGGGGGUG CCCCCACCACCACGCCCGUU
hsa-miR-1269a CUGGACUGAGCCGUGCUACUGG AGUAGCACGGCUCAGUCCAGUU
hsa-miR-1269b CUGGACUGAGCCAUGCUACUGG AGUAGCAUGGCUCAGUCCAGUU
hsa-miR-127 UCGGAUCCGUCUGAGCUUGGCU CUGAAGCUCAGAGGGCUCUGAU
hsa-miR-1270 CUGGAGAUAUGGAAGAGCUGUGU ACAGCUCUUCCAUAUCUCCAGUU
hsa-miR-1271 AGUGCCUGCUAUGUGCCAGGCA CUUGGCACCUAGCAAGCACUCA
hsa-miR-1272 GAUGAUGAUGGCAGCAAAUUCUGAAA UCAGAAUUUGCUGCCAUCAUCAUCUU
hsa-miR-1273a GGGCGACAAAGCAAGACUCUUUCUU GAAAGAGUCUUGCUUUGUCGCCCUU
hsa-miR-1273c GGCGACAAAACGAGACCCUGUC CAGGGUCUCGUUUUGUCGCCUU
hsa-miR-1273d GAACCCAUGAGGUUGAGGCUGCAGU UGCAGCCUCAACCUCAUGGGUUCUU
hsa-miR-1273e UUGCUUGAACCCAGGAAGUGGA CACUUCCUGGGUUCAAGCAAUU
hsa-miR-1273f GGAGAUGGAGGUUGCAGUG CUGCAACCUCCAUCUCCUU
hsa-miR-1273g GGUGGUUGAGGCUGCAGUAAGU ACCACUGCACUCCAGCCUGAG
hsa-miR-1273h CUGGGAGGUCAAGGCUGCAGU CUGCAGACUCGACCUCCCAGGC
hsa-miR-1275 GUGGGGGAGAGGCUGUC CAGCCUCUCCCCCACUU
hsa-miR-1276 UAAAGAGCCCUGUGGAGACA UCUCCACAGGGCUCUUUAUU
hsa-miR-1277 UACGUAGAUAUAUAUGUAUUUU AAAUAUAUAUAUAUAUGUACGUAU
hsa-miR-1278 UAGUACUGUGCAUAUCAUCUAU AGAUGAUAUGCACAGUACUAUU
hsa-miR-1279 UCAUAUUGCUUCUUUCU AAAGAAGCAAUAUGAUU
hsa-miR-128-1 UCACAGUGAACCGGUCUCUUU CGGGGCCGUAGCACUGUCUGAGA
hsa-miR-128-2 UCACAGUGAACCGGUCUCUUU GGGGGCCGAUACACUGUACGAGA
hsa-miR-1281 UCGCCUCCUCCUCUCCC GAGAGGAGGAGGCGAUU
hsa-miR-1282 UCGUUUGCCUUUUUCUGCUU GCAGAAAAAGGCAAACGAUU
hsa-miR-1283 UCUACAAAGGAAAGCGCUUUCU AAAGCGCUUUCCUUUGUAGAUU
hsa-miR-1284 UCUAUACAGACCCUGGCUUUUC AAAGCCAGGGUCUGUAUAGAUU
hsa-miR-1285 UCUGGGCAACAAAGUGAGACCU GAUCUCACUUUGUUGCCCAGG
hsa-miR-1286 UGCAGGACCAAGAUGAGCCCU GGCUCAUCUUGGUCCUGCAUU
hsa-miR-1287 CUCUAGCCACAGAUGCAGUGAU UGCUGGAUCAGUGGUUCGAGUC
hsa-miR-1288 UGGACUGCCCUGAUCUGGAGA GCAGAUCAGGACUGUAACUCACC
hsa-miR-1289 UGGAGUCCAGGAAUCUGCAUUUU AAUGCAGAUUCCUGGACUCCAUU
hsa-miR-129-1 CUUUUUGCGGUCUGGGCUUGC AAGCCCUUACCCCAAAAAGUAU
hsa-miR-129-2 CUUUUUGCGGUCUGGGCUUGC AAGCCCUUACCCCAAAAAGCAU
hsa-miR-1290 UGGAUUUUUGGAUCAGGGA CCUGAUCCAAAAAUCCAUU
hsa-miR-1291 UGGCCCUGACUGAAGACCAGCAGU UGCUGGUCUUCAGUCAGGGCCAUU
hsa-miR-1292 UGGGAACGGGUUCCGGCAGACGCUG UCGCGCCCCGGCUCCCGUUC
hsa-miR-1293 UGGGUGGUCUGGAGAUUUGUGC ACAAAUCUCCAGACCACCCAUU
hsa-miR-1294 UGUGAGGUUGGCAUUGUUGUCU ACAACAAUGCCAACCUCACAUU
hsa-miR-1295a UUAGGCCGCAGAUCUGGGUGA ACCCAGAUCUGCGGCCUAAUU
hsa-miR-1295b AAUAGGCCACGGAUCUGGGCAA CACCCAGAUCUGCGGCCUAAU
hsa-miR-1296 UUAGGGCCCUGGCUCCAUCUCC GAGUGGGGCUUCGACCCUAACC
hsa-miR-1297 UUCAAGUAAUUCAGGUG CCUGAAUUACUUGAAUU
hsa-miR-1298 CAUCUGGGCAACUGACUGAAC UUCAUUCGGCUGUCCAGAUGUA
hsa-miR-1299 UUCUGGAAUUCUGUGUGAGGGA CCUCACACAGAAUUCCAGAAUU
hsa-miR-1301 CGCUCUAGGCACCGCAGCA UUGCAGCUGCCUGGGAGUGACUUC
hsa-miR-1302 UUGGGACAUACUUAUGCUAAA UAGCAUAAGUAUGUCCCAAUU
hsa-miR-1303 UUUAGAGACGGGGUCUUGCUCU AGCAAGACCCCGUCUCUAAAUU
hsa-miR-1304 UUUGAGGCUACAGUGAGAUGUG UCUCACUGUAGCCUCGAACCCC
hsa-miR-1305 UUUUCAACUCUAAUGGGAGAGA UCUCCCAUUAGAGUUGAAAAUU
hsa-miR-1306 CCACCUCCCCUGCAAACGUCCA ACGUUGGCUCUGGUGGUG
hsa-miR-1307 ACUCGGCGUGGCGUCGGUCGUG UCGACCGGACCUCGACCGGCU
hsa-miR-130a UUCACAUUGUGCUACUGUCUGC CAGUGCAAUGUUAAAAGGGCAU
hsa-miR-130b CAGUGCAAUGAUGAAAGGGCAU ACUCUUUCCCUGUUGCACUAC
hsa-miR-132 UAACAGUCUACAGCCAUGGUCG ACCGUGGCUUUCGAUUGUUACU
hsa-miR-1321 CAGGGAGGUGAAUGUGAU CACAUUCACCUCCCUGUU
hsa-miR-1322 GAUGAUGCUGCUGAUGCUG GCAUCAGCAGCAUCAUCUU
hsa-miR-1323 UCAAAACUGAGGGGCAUUUUCU AAAAUGCCCCUCAGUUUUGAUU
hsa-miR-1324 CCAGACAGAAUUCUAUGCACUUUC AAGUGCAUAGAAUUCUGUCUGGUU
hsa-miR-133a AGCUGGUAAAAUGGAACCAAAU UUUGGUCCCCUUCAACCAGCUG
hsa-miR-133b UUUGGUCCCCUUCAACCAGCUA GCUGGUUGAAGGGGACCAAAUU
hsa-miR-134 UGUGACUGGUUGACCAGAGGGG CCUGUGGGCCACCUAGUCACCAA
hsa-miR-1343 CUCCUGGGGCCCGCACUCUCGC UGGGGAGCGGCCCCCGGGUGGG
hsa-miR-135a UAUAGGGAUUGGAGCCGUGGCG UAUGGCUUUUUAUUCCUAUGUGA
hsa-miR-135b AUGUAGGGCUAAAAGCCAUGGG UAUGGCUUUUCAUUCCUAUGUGA
hsa-miR-136 CAUCAUCGUCUCAAAUGAGUCU ACUCCAUUUGUUUUGAUGAUGGA
hsa-miR-137 UUAUUGCUUAAGAAUACGCGUAG ACGCGUAUUCUUAAGCAAUAAUU
hsa-miR-138-1 AGCUGGUGUUGUGAAUCAGGCCG GCUACUUCACAACACCAGGGCC
hsa-miR-138-2 AGCUGGUGUUGUGAAUCAGGCCG GCUAUUUCACGACACCAGGGUU
hsa-miR-139 UCUACAGUGCACGUGUCUCCAGU UGGAGACGCGGCCCUGUUGGAGU
hsa-miR-140 CAGUGGUUUUACCCUAUGGUAG UACCACAGGGUAGAACCACGG
hsa-miR-141 UAACACUGUCUGGUAAAGAUGG CAUCUUCCAGUACAGUGUUGGA
hsa-miR-142 CAUAAAGUAGAAAGCACUACU UGUAGUGUUUCCUACUUUAUGGA
hsa-miR-143 GGUGCAGUGCUGCAUCUCUGGU UGAGAUGAAGCACUGUAGCUC
hsa-miR-144 UACAGUAUAGAUGAUGUACU GGAUAUCAUCAUAUACUGUAAG
hsa-miR-145 GUCCAGUUUUCCCAGGAAUCCCU GGAUUCCUGGAAAUACUGUUCU
hsa-miR-1468 CUCCGUUUGCCUGUUUCGCUG AGCAAAAUAAGCAAAUGGAAAA
hsa-miR-1469 CUCGGCGCGGGGCGCGGGCUCC AGCCCGCGCCCCGCGCCGAGUU
hsa-miR-146a UGAGAACUGAAUUCCAUGGGUU CCUCUGAAAUUCAGUUCUUCAG
hsa-miR-146b UGCCCUGUGGACUCAGUUCUGG UGAGAACUGAAUUCCAUAGGCU
hsa-miR-1470 GCCCUCCGCCCGUGCACCCCG GGGUGCACGGGCGGAGGGCUU
hsa-miR-1471 GCCCGCGUGUGGAGCCAGGUGU ACCUGGCUCCACACGCGGGCUU
hsa-miR-147a GUGUGUGGAAAUGCUUCUGC AGAAGCAUUUCCACACACUU
hsa-miR-147b GUGUGCGGAAAUGCUUCUGCUA GCAGAAGCAUUUCCGCACACUU
hsa-miR-148a AAAGUUCUGAGACACUCCGACU UCAGUGCACUACAGAACUUUGU
hsa-miR-148b AAGUUCUGUUAUACACUCAGGC UCAGUGCAUCACAGAACUUUGU
hsa-miR-149 AGGGAGGGACGGGGGCUGUGC UCUGGCUCCGUGUCUUCACUCCC
hsa-miR-150 CUGGUACAGGCCUGGGGGACAG UCUCCCAACCCUUGUACCAGUG
hsa-miR-151a UCGAGGAGCUCACAGUCUAGU CUAGACUGAAGCUCCUUGAGG
hsa-miR-151b UCGAGGAGCUCACAGUCU ACUGUGAGCUCCUCGAUU
hsa-miR-152 AGGUUCUGUGAUACACUCCGACU UCAGUGCAUGACAGAACUUGG
hsa-miR-153 UCAUUUUUGUGAUGUUGCAGCU UUGCAUAGUCACAAAAGUGAUC
hsa-miR-1537 AGCUGUAAUUAGUCAGUUUUCU AAAACCGUCUAGUUACAGUUGU
hsa-miR-1538 CGGCCCGGGCUGCUGCUGUUCCU GAACAGCAGCAGCCCGGGCCGUU
hsa-miR-1539 UCCUGCGCGUCCCAGAUGCCC GCAUCUGGGACGCGCAGGAUU
hsa-miR-154 AAUCAUACACGGUUGACCUAUU UAGGUUAUCCGUGUUGCCUUCG
hsa-miR-155 CUCCUACAUAUUAGCAUUAACA UUAAUGCUAAUCGUGAUAGGGGU
hsa-miR-1587 UUGGGCUGGGCUGGGUUGGG CAACCCAGCCCAGCCCAAUU
hsa-miR-15a CAGGCCAUAUUGUGCUGCCUCA UAGCAGCACAUAAUGGUUUGUG
hsa-miR-15b CGAAUCAUUAUUUGCUGCUCUA UAGCAGCACAUCAUGGUUUACA
hsa-miR-16-1 UAGCAGCACGUAAAUAUUGGCG CCAGUAUUAACUGUGCUGCUGA
hsa-miR-16-2 UAGCAGCACGUAAAUAUUGGCG CCAAUAUUACUGUGCUGCUUUA
hsa-miR-17 ACUGCAGUGAAGGCACUUGUAG CAAAGUGCUUACAGUGCAGGUAG
hsa-miR-181a-1 AACAUUCAACGCUGUCGGUGAGU ACCAUCGACCGUUGAUUGUACC
hsa-miR-181a-2 AACAUUCAACGCUGUCGGUGAGU ACCACUGACCGUUGACUGUACC
hsa-miR-181b-1 AACAUUCAUUGCUGUCGGUGGGU CUCACUGAACAAUGAAUGCAA
hsa-miR-181b-2 AACAUUCAUUGCUGUCGGUGGGU CUCACUGAUCAAUGAAUGCA
hsa-miR-181c AACCAUCGACCGUUGAGUGGAC AACAUUCAACCUGUCGGUGAGU
hsa-miR-181d CCACCGGGGGAUGAAUGUCAC AACAUUCAUUGUUGUCGGUGGGU
hsa-miR-182 UUUGGCAAUGGUAGAACUCACACU UGGUUCUAGACUUGCCAACUA
hsa-miR-1825 UCCAGUGCCCUCCUCUCC AGAGGAGGGCACUGGAUU
hsa-miR-1827 UGAGGCAGUAGAUUGAAU UCAAUCUACUGCCUCAUU
hsa-miR-183 UAUGGCACUGGUAGAAUUCACU GUGAAUUACCGAAGGGCCAUAA
hsa-miR-184 UGGACGGAGAACUGAUAAGGGU CCUUAUCAGUUCUCCGUCCAUU
hsa-miR-185 AGGGGCUGGCUUUCCUCUGGUC UGGAGAGAAAGGCAGUUCCUGA
hsa-miR-186 CAAAGAAUUCUCCUUUUGGGCU GCCCAAAGGUGAAUUUUUUGGG
hsa-miR-187 UCGUGUCUUGUGUUGCAGCCGG GGCUACAACACAGGACCCGGGC
hsa-miR-188 CAUCCCUUGCAUGGUGGAGGG CUCCCACAUGCAGGGUUUGCA
hsa-miR-18a UAAGGUGCAUCUAGUGCAGAUAG ACUGCCCUAAGUGCUCCUUCUGG
hsa-miR-18b UAAGGUGCAUCUAGUGCAGUUAG UGCCCUAAAUGCCCCUUCUGGC
hsa-miR-1908 CGGCGGGGACGGCGAUUGGUC CCGGCCGCCGGCUCCGCCCCG
hsa-miR-1909 CGCAGGGGCCGGGUGCUCACCG UGAGUGCCGGUGCCUGCCCUG
hsa-miR-190a UGAUAUGUUUGAUAUAUUAGGU CUAUAUAUCAAACAUAUUCCU
hsa-miR-190b UGAUAUGUUUGAUAUUGGGUU CCCAAUAUCAAACAUAUCAUU
hsa-miR-191 GCUGCGCUUGGAUUUCGUCCCC CAACGGAAUCCCAAAAGCAGCUG
hsa-miR-1910 CCAGUCCUGUGCCUGCCGCCU GAGGCAGAAGCAGGAUGACA
hsa-miR-1911 CACCAGGCAUUGUGGUCUCC UGAGUACCGCCAUGUCUGUUGGG
hsa-miR-1912 UACCCAGAGCAUGCAGUGUGAA CACACUGCAUGCUCUGGGUAUU
hsa-miR-1913 UCUGCCCCCUCCGCUGCUGCCA GCAGCAGCGGAGGGGGCAGAUU
hsa-miR-1914 CCCUGUGCCCGGCCCACUUCUG GGAGGGGUCCCGCACUGGGAGG
hsa-miR-1915 ACCUUGCCUUGCUGCCCGGGCC CCCCAGGGCGACGCGGCGGG
hsa-miR-192 CUGCCAAUUCCAUAGGUCACAG CUGACCUAUGAAUUGACAGCC
hsa-miR-193a UGGGUCUUUGCGGGCGAGAUGA AACUGGCCUACAAAGUCCCAGU
hsa-miR-193b CGGGGUUUUGAGGGCGAGAUGA AACUGGCCCUCAAAGUCCCGCU
hsa-miR-194 UGUAACAGCAACUCCAUGUGGA CCAGUGGGGCUGCUGUUAUCUG
hsa-miR-195 UAGCAGCACAGAAAUAUUGGC CCAAUAUUGGCUGUGCUGCUCC
hsa-miR-196a UAGGUAGUUUCAUGUUGUUGGG CGGCAACAAGAAACUGCCUGAG
hsa-miR-196b UCGACAGCACGACACUGCCUUC UAGGUAGUUUCCUGUUGUUGGG
hsa-miR-197 CGGGUAGAGAGGGCAGUGGGAGG UUCACCACCUUCUCCACCCAGC
hsa-miR-1972 UCAGGCCAGGCACAGUGGCUCA AGCCACUGUGCCUGGCCUGAUU
hsa-miR-1973 ACCGUGCAAAGGUAGCAUA UGCUACCUUUGCACGGUUU
hsa-miR-1976 CCUCCUGCCCUCCUUGCUGU AGCAAGGAGGGCAGGAGGUU
hsa-miR-198 GGUCCAGAGGGGAGAUAGGUUC ACCUAUCUCCCCUCUGGACCUU
hsa-miR-199a ACAGUAGUCUGCACAUUGGUUA CCCAGUGUUCAGACUACCUGUUC
hsa-miR-199b CCCAGUGUUUAGACUAUCUGUUC ACAGUAGUCUGCACAUUGGUUA
hsa-miR-19a UGUGCAAAUCUAUGCAAAACUGA AGUUUUGCAUAGUUGCACUACA
hsa-miR-19b-1 UGUGCAAAUCCAUGCAAAACUGA AGUUUUGCAGGUUUGCAUCCAGC
hsa-miR-19b-2 UGUGCAAAUCCAUGCAAAACUGA AGUUUUGCAGGUUUGCAUUUCA
hsa-miR-200a UAACACUGUCUGGUAACGAUGU CAUCUUACCGGACAGUGCUGGA
hsa-miR-200b CAUCUUACUGGGCAGCAUUGGA UAAUACUGCCUGGUAAUGAUGA
hsa-miR-200c UAAUACUGCCGGGUAAUGAUGGA CGUCUUACCCAGCAGUGUUUGG
hsa-miR-202 UUCCUAUGCAUAUACUUCUUUG AGAGGUAUAGGGCAUGGGAA
hsa-miR-203a AGUGGUUCUUAACAGUUCAACAGUU GUGAAAUGUUUAGGACCACUAG
hsa-miR-203b UAGUGGUCCUAAACAUUUCACA UUGAACUGUUAAGAACCACUGGA
hsa-miR-204 GCUGGGAAGGCAAAGGGACGU UUCCCUUUGUCAUCCUAUGCCU
hsa-miR-205 UCCUUCAUUCCACCGGAGUCUG GAUUUCAGUGGAGUGAAGUUC
hsa-miR-2052 UGUUUUGAUAACAGUAAUGU AUUACUGUUAUCAAAACAUU
hsa-miR-2053 GUGUUAAUUAAACCUCUAUUUAC AAAUAGAGGUUUAAUUAACACUU
hsa-miR-2054 CUGUAAUAUAAAUUUAAUUUAUU UAAAUUAAAUUUAUAUUACAGUU
hsa-miR-206 UGGAAUGUAAGGAAGUGUGUGG ACACACUUCCUUACAUUCCAUU
hsa-miR-208a AUAAGACGAGCAAAAAGCUUGU GAGCUUUUGGCCCGGGUUAUAC
hsa-miR-208b AAGCUUUUUGCUCGAAUUAUGU AUAAGACGAACAAAAGGUUUGU
hsa-miR-20a UAAAGUGCUUAUAGUGCAGGUAG ACUGCAUUAUGAGCACUUAAAG
hsa-miR-20b CAAAGUGCUCAUAGUGCAGGUAG ACUGUAGUAUGGGCACUUCCAG
hsa-miR-21 UAGCUUAUCAGACUGAUGUUGA CAACACCAGUCGAUGGGCUGU
hsa-miR-210 AGCCCCUGCCCACCGCACACUG CUGUGCGUGUGACAGCGGCUGA
hsa-miR-211 GCAGGGACAGCAAAGGGGUGC UUCCCUUUGUCAUCCUUCGCCU
hsa-miR-2110 UUGGGGAAACGGCCGCUGAGUG CUCAGCGGCCGUUUCCCCAAUU
hsa-miR-2113 AUUUGUGCUUGGCUCUGUCAC GACAGAGCCAAGCACAAAUUU
hsa-miR-2114 UAGUCCCUUCCUUGAAGCGGUC CGAGCCUCAAGCAAGGGACUU
hsa-miR-2115 CAUCAGAAUUCAUGGAGGCUAG AGCUUCCAUGACUCCUGAUGGA
hsa-miR-2116 GGUUCUUAGCAUAGGAGGUCU CCUCCCAUGCCAAGAACUCCC
hsa-miR-2117 UGUUCUCUUUGCCAAGGACAG GUCCUUGGCAAAGAGAACAUU
hsa-miR-212 UAACAGUCUCCAGUCACGGCC ACCUUGGCUCUAGACUGCUUACU
hsa-miR-214 UGCCUGUCUACACUUGCUGUGC ACAGCAGGCACAGACAGGCAGU
hsa-miR-215 UCUGUCAUUUCUUUAGGCCAAUA AUGACCUAUGAAUUGACAGAC
hsa-miR-216a UAAUCUCAGCUGGCAACUGUGA UCACAGUGGUCUCUGGGAUUAU
hsa-miR-216b AAAUCUCUGCAGGCAAAUGUGA ACACACUUACCCGUAGAGAUUCUA
hsa-miR-217 UACUGCAUCAGGAACUGAUUGGA CAAUCAGUUCCUGAUGCAGUAUU
hsa-miR-218-1 UUGUGCUUGAUCUAACCAUGU AUGGUUCCGUCAAGCACCAUGG
hsa-miR-218-2 UUGUGCUUGAUCUAACCAUGU CAUGGUUCUGUCAAGCACCGCG
hsa-miR-219a-1 UGAUUGUCCAAACGCAAUUCU AGAGUUGAGUCUGGACGUCCCG
hsa-miR-219a-2 UGAUUGUCCAAACGCAAUUCU AGAAUUGUGGCUGGACAUCUGU
hsa-miR-219b AGAUGUCCAGCCACAAUUCUCG AGAAUUGCGUUUGGACAAUCAGU
hsa-miR-22 AGUUCUUCAGUGGCAAGCUUUA AAGCUGCCAGUUGAAGAACUGU
hsa-miR-221 AGCUACAUUGUCUGCUGGGUUUC ACCUGGCAUACAAUGUAGAUUU
hsa-miR-222 AGCUACAUCUGGCUACUGGGU CUCAGUAGCCAGUGUAGAUCCU
hsa-miR-223 CGUGUAUUUGACAAGCUGAGUU UGUCAGUUUGUCAAAUACCCCA
hsa-miR-224 AAAAUGGUGCCCUAGUGACUACA CAAGUCACUAGUGGUUCCGUU
hsa-miR-2276 GCCCUCUGUCACCUUGCAGACG UCUGCAAGUGUCAGAGGCGAGG
hsa-miR-2277 AGCGCGGGCUGAGCGCUGCCAGUC UGACAGCGCCCUGCCUGGCUC
hsa-miR-2278 GAGAGCAGUGUGUGUUGCCUGG AGGCAACACACACUGCUCUCUU
hsa-miR-2355 AUCCCCAGAUACAAUGGACAA AUUGUCCUUGCUGUUUGGAGAU
hsa-miR-2392 UAGGAUGGGGGUGAGAGGUG CCUCUCACCCCCAUCCUAUU
hsa-miR-23a AUCACAUUGCCAGGGAUUUCC GGGGUUCCUGGGGAUGGGAUUU
hsa-miR-23b AUCACAUUGCCAGGGAUUACC UGGGUUCCUGGCAUGCUGAUUU
hsa-miR-23c AUCACAUUGCCAGUGAUUACCC GUAAUCACUGGCAAUGUGAUUU
hsa-miR-24-1 UGGCUCAGUUCAGCAGGAACAG UGCCUACUGAGCUGAUAUCAGU
hsa-miR-24-2 UGGCUCAGUUCAGCAGGAACAG UGCCUACUGAGCUGAAACACAG
hsa-miR-2467 AGCAGAGGCAGAGAGGCUCAGG UGAGGCUCUGUUAGCCUUGGCUC
hsa-miR-25 AGGCGGAGACUUGGGCAAUUG CAUUGCACUUGUCUCGGUCUGA
hsa-miR-2681 GUUUUACCACCUCCAGGAGACU UAUCAUGGAGUUGGUAAAGCAC
hsa-miR-2682 CGCCUCUUCAGCGCUGUCUUCC CAGGCAGUGACUGUUCAGACGUC
hsa-miR-26a-1 UUCAAGUAAUCCAGGAUAGGCU CCUAUUCUUGGUUACUUGCACG
hsa-miR-26a-2 UUCAAGUAAUCCAGGAUAGGCU CCUAUUCUUGAUUACUUGUUUC
hsa-miR-26b UUCAAGUAAUUCAGGAUAGGU CCUGUUCUCCAUUACUUGGCUC
hsa-miR-27a UUCACAGUGGCUAAGUUCCGC AGGGCUUAGCUGCUUGUGAGCA
hsa-miR-27b UUCACAGUGGCUAAGUUCUGC AGAGCUUAGCUGAUUGGUGAAC
hsa-miR-28 CACUAGAUUGUGAGCUCCUGGA AAGGAGCUCACAGUCUAUUGAG
hsa-miR-2861 GGGGCCUGGCGGUGGGCGG GCCCACCGCCAGGCCCCUU
hsa-miR-2909 GUUAGGGCCAACAUCUCUUGG AAGAGAUGUUGGCCCUAACUU
hsa-miR-296 GAGGGUUGGGUGGAGGCUCUCC AGGGCCCCCCCUCAAUCCUGU
hsa-miR-297 AUGUAUGUGUGCAUGUGCAUG UGCACAUGCACACAUACAUUU
hsa-miR-298 AGCAGAAGCAGGGAGGUUCUCCCA GGAGAACCUCCCUGCUUCUGCUUU
hsa-miR-299 UGGUUUACCGUCCCACAUACAU UAUGUGGGAUGGUAAACCGCUU
hsa-miR-29a ACUGAUUUCUUUUGGUGUUCAG UAGCACCAUCUGAAAUCGGUUA
hsa-miR-29b-1 UAGCACCAUUUGAAAUCAGUGUU GCUGGUUUCAUAUGGUGGUUUAGA
hsa-miR-29b-2 UAGCACCAUUUGAAAUCAGUGUU CUGGUUUCACAUGGUGGCUUAG
hsa-miR-29c UGACCGAUUUCUCCUGGUGUUC UAGCACCAUUUGAAAUCGGUUA
hsa-miR-300 UAUACAAGGGCAGACUCUCUCU AGAGAGUCUGCCCUUGUAUAUU
hsa-miR-301a GCUCUGACUUUAUUGCACUACU CAGUGCAAUAGUAUUGUCAAAGC
hsa-miR-301b CAGUGCAAUGAUAUUGUCAAAGC GCUCUGACGAGGUUGCACUACU
hsa-miR-302a UAAGUGCUUCCAUGUUUUGGUGA ACUUAAACGUGGAUGUACUUGCU
hsa-miR-302b UAAGUGCUUCCAUGUUUUAGUAG ACUUUAACAUGGAAGUGCUUUC
hsa-miR-302c UUUAACAUGGGGGUACCUGCUG UAAGUGCUUCCAUGUUUCAGUGG
hsa-miR-302d ACUUUAACAUGGAGGCACUUGC UAAGUGCUUCCAUGUUUGAGUGU
hsa-miR-302e UAAGUGCUUCCAUGCUU GCAUGGAAGCACUUAUU
hsa-miR-302f UAAUUGCUUCCAUGUUU ACAUGGAAGCAAUUAUU
hsa-miR-3064 UUGCCACACUGCAACACCUUACA UCUGGCUGUUGUGGUGUGCAA
hsa-miR-3065 UCAGCACCAGGAUAUUGUUGGAG UCAACAAAAUCACUGAUGCUGGA
hsa-miR-3074 GAUAUCAGCUCAGUAGGCACCG GUUCCUGCUGAACUGAGCCAG
hsa-miR-30a CUUUCAGUCGGAUGUUUGCAGC UGUAAACAUCCUCGACUGGAAG
hsa-miR-30b UGUAAACAUCCUACACUCAGCU CUGGGAGGUGGAUGUUUACUUC
hsa-miR-30c-1 UGUAAACAUCCUACACUCUCAGC CUGGGAGAGGGUUGUUUACUCC
hsa-miR-30c-2 UGUAAACAUCCUACACUCUCAGC CUGGGAGAAGGCUGUUUACUCU
hsa-miR-30d UGUAAACAUCCCCGACUGGAAG CUUUCAGUCAGAUGUUUGCUGC
hsa-miR-30e UGUAAACAUCCUUGACUGGAAG CUUUCAGUCGGAUGUUUACAGC
hsa-miR-31 UGCUAUGCCAACAUAUUGCCAU AGGCAAGAUGCUGGCAUAGCU
hsa-miR-3115 AUAUGGGUUUACUAGUUGGU CAACUAGUAAACCCAUAUUU
hsa-miR-3116 UGCCUGGAACAUAGUAGGGACU UCCCUACUAUGUUCCAGGCAUU
hsa-miR-3117 AUAGGACUCAUAUAGUGCCAG AGACACUAUACGAGUCAUAU
hsa-miR-3118 UGUGACUGCAUUAUGAAAAUUCU AAUUUUCAUAAUGCAGUCACAUU
hsa-miR-3119 UGGCUUUUAACUUUGAUGGC CAUCAAAGUUAAAAGCCAUU
hsa-miR-3120 CCUGUCUGUGCCUGCUGUACA CACAGCAAGUGUAGACAGGCA
hsa-miR-3121 UCCUUUGCCUAUUCUAUUUAAG UAAAUAGAGUAGGCAAAGGACA
hsa-miR-3122 GUUGGGACAAGAGGACGGUCUU GACCGUCCUCUUGUCCCAACUU
hsa-miR-3123 CAGAGAAUUGUUUAAUC UUAAACAAUUCUCUGUU
hsa-miR-3124 UUCGCGGGCGAAGGCAAAGUC ACUUUCCUCACUCCCGUGAAGU
hsa-miR-3125 UAGAGGAAGCUGUGGAGAGA UCUCCACAGCUUCCUCUAUU
hsa-miR-3126 CAUCUGGCAUCCGUCACACAGA UGAGGGACAGAUGCCAGAAGCA
hsa-miR-3127 UCCCCUUCUGCAGGCCUGCUGG AUCAGGGCUUGUGGAAUGGGAAG
hsa-miR-3128 UCUGGCAAGUAAAAAACUCUCAU GAGAGUUUUUUACUUGCCAGAUU
hsa-miR-3129 GCAGUAGUGUAGAGAUUGGUUU AAACUAAUCUCUACACUGCUGC
hsa-miR-3130 GCUGCACCGGAGACUGGGUAA UACCCAGUCUCCGGUGCAGCC
hsa-miR-3131 UCGAGGACUGGUGGAAGGGCCUU GGCCCUUCCACCAGUCCUCGAUU
hsa-miR-3132 UGGGUAGAGAAGGAGCUCAGAGGA CUCUGAGCUCCUUCUCUACCCAUU
hsa-miR-3133 UAAAGAACUCUUAAAACCCAAU UGGGUUUUAAGAGUUCUUUAUU
hsa-miR-3134 UGAUGGAUAAAAGACUACAUAUU UAUGUAGUCUUUUAUCCAUCAUU
hsa-miR-3135a UGCCUAGGCUGAGACUGCAGUG CUGCAGUCUCAGCCUAGGCAUU
hsa-miR-3135b GGCUGGAGCGAGUGCAGUGGUG CCACUGCACUCGCUCCAGCCUU
hsa-miR-3136 CUGACUGAAUAGGUAGGGUCAUU UGGCCCAACCUAUUCAGUUAGU
hsa-miR-3137 UCUGUAGCCUGGGAGCAAUGGGGU CCCAUUGCUCCCAGGCUACAGAUU
hsa-miR-3138 UGUGGACAGUGAGGUAGAGGGAGU UCCCUCUACCUCACUGUCCACAUU
hsa-miR-3139 UAGGAGCUCAACAGAUGCCUGUU CAGGCAUCUGUUGAGCUCCUAUU
hsa-miR-3140 ACCUGAAUUACCAAAAGCUUU AGCUUUUGGGAAUUCAGGUAGU
hsa-miR-3141 GAGGGCGGGUGGAGGAGGA CUCCUCCACCCGCCCUCUU
hsa-miR-3142 AAGGCCUUUCUGAACCUUCAGA UGAAGGUUCAGAAAGGCCUUUU
hsa-miR-3143 AUAACAUUGUAAAGCGCUUCUUUCG AAAGAAGCGCUUUACAAUGUUAUUU
hsa-miR-3144 AUAUACCUGUUCGGUCUCUUUA AGGGGACCAAAGAGAUAUAUAG
hsa-miR-3145 AGAUAUUUUGAGUGUUUGGAAUUG AACUCCAAACACUCAAAACUCA
hsa-miR-3146 CAUGCUAGGAUAGAAAGAAUGG AUUCUUUCUAUCCUAGCAUGUU
hsa-miR-3147 GGUUGGGCAGUGAGGAGGGUGUGA ACACCCUCCUCACUGCCCAACCUU
hsa-miR-3148 UGGAAAAAACUGGUGUGUGCUU GCACACACCAGUUUUUUCCAUU
hsa-miR-3149 UUUGUAUGGAUAUGUGUGUGUAU ACACACACAUAUCCAUACAAAUU
hsa-miR-3150a CAACCUCGACGAUCUCCUCAGC CUGGGGAGAUCCUCGAGGUUGG
hsa-miR-3150b CAACCUCGAGGAUCUCCCCAGC UGAGGAGAUCGUCGAGGUUGG
hsa-miR-3151 GGUGGGGCAAUGGGAUCAGGU CCUGAUCCCACAGCCCACCU
hsa-miR-3152 AUUGCCUCUGUUCUAACACAAG UGUGUUAGAAUAGGGGCAAUAA
hsa-miR-3153 GGGGAAAGCGAGUAGGGACAUUU AUGUCCCUACUCGCUUUCCCCUU
hsa-miR-3154 CAGAAGGGGAGUUGGGAGCAGA UGCUCCCAACUCCCCUUCUGUU
hsa-miR-3155a CCAGGCUCUGCAGUGGGAACU UUCCCACUGCAGAGCCUGGUU
hsa-miR-3155b CCAGGCUCUGCAGUGGGA CCACUGCAGAGCCUGGUU
hsa-miR-3156 CUCCCACUUCCAGAUCUUUCU AAAGAUCUGGAAGUGGGAGACA
hsa-miR-3157 CUGCCCUAGUCUAGCUGAAGCU UUCAGCCAGGCUAGUGCAGUCU
hsa-miR-3158 AAGGGCUUCCUCUCUGCAGGAC CCUGCAGAGAGGAAGCCCUUC
hsa-miR-3159 UAGGAUUACAAGUGUCGGCCAC GGCCGACACUUGUAAUCCUAUU
hsa-miR-3160 AGAGCUGAGACUAGAAAGCCCA GGCUUUCUAGUCUCAGCUCUCC
hsa-miR-3161 CUGAUAAGAACAGAGGCCCAGAU CUGGGCCUCUGUUCUUAUCAGUU
hsa-miR-3162 UUAGGGAGUAGAAGGGUGGGGAG UCCCUACCCCUCCACUCCCCA
hsa-miR-3163 UAUAAAAUGAGGGCAGUAAGAC CUUACUGCCCUCAUUUUAUAUU
hsa-miR-3164 UGUGACUUUAAGGGAAAUGGCG CCAUUUCCCUUAAAGUCACAUU
hsa-miR-3165 AGGUGGAUGCAAUGUGACCUCA AGGUCACAUUGCAUCCACCUUU
hsa-miR-3166 CGCAGACAAUGCCUACUGGCCUA GGCCAGUAGGCAUUGUCUGCGUU
hsa-miR-3167 AGGAUUUCAGAAAUACUGGUGU ACCAGUAUUUCUGAAAUCCUUU
hsa-miR-3168 GAGUUCUACAGUCAGAC CUGACUGUAGAACUCUU
hsa-miR-3169 UAGGACUGUGCUUGGCACAUAG AUGUGCCAAGCACAGUCCUAUU
hsa-miR-3170 CUGGGGUUCUGAGACAGACAGU UGUCUGUCUCAGAACCCCAGUU
hsa-miR-3171 AGAUGUAUGGAAUCUGUAUAUAUC UAUAUACAGAUUCCAUACAUCUUU
hsa-miR-3173 AAAGGAGGAAAUAGGCAGGCCA UGCCCUGCCUGUUUUCUCCUUU
hsa-miR-3174 UAGUGAGUUAGAGAUGCAGAGCC CUCUGCAUCUCUAACUCACUAUU
hsa-miR-3175 CGGGGAGAGAACGCAGUGACGU GUCACUGCGUUCUCUCCCCGUU
hsa-miR-3176 ACUGGCCUGGGACUACCGG GGUAGUCCCAGGCCAGUUU
hsa-miR-3177 UGUGUACACACGUGCCAGGCGCU UGCACGGCACUGGGGACACGU
hsa-miR-3178 GGGGCGCGGCCGGAUCG AUCCGGCCGCGCCCCUU
hsa-miR-3179 AGAAGGGGUGAAAUUUAAACGU GUUUAAAUUUCACCCCUUCUUU
hsa-miR-3180 CUUCCAGACGCUCCGCCCCACGUCG UGGGGCGGAGCUUCCGGAGGCC
hsa-miR-3181 AUCGGGCCCUCGGCGCCGG GGCGCCGAGGGCCCGAUUU
hsa-miR-3182 GCUUCUGUAGUGUAGUC CUACACUACAGAAGCUU
hsa-miR-3183 GCCUCUCUCGGAGUCGCUCGGA CGAGCGACUCCGAGAGAGGCUU
hsa-miR-3184 AAAGUCUCGCUCUCUGCCCCUCA UGAGGGGCCUCAGACCGAGCUUUU
hsa-miR-3185 AGAAGAAGGCGGUCGGUCUGCGG GCAGACCGACCGCCUUCUUCUUU
hsa-miR-3186 CAGGCGUCUGUCUACGUGGCUU UCACGCGGAGAGAUGGCUUUG
hsa-miR-3187 UUGGCCAUGGGGCUGCGCGG CCUGGGCAGCGUGUGGCUGAAGG
hsa-miR-3188 AGAGGCUUUGUGCGGAUACGGGG CCGUAUCCGCACAAAGCCUCUUU
hsa-miR-3189 CCCUUGGGUCUGAUGGGGUAG UGCCCCAUCUGUGCCCUGGGUAGGA
hsa-miR-3190 UGUGGAAGGUAGACGGCCAGAGA UCUGGCCAGCUACGUCCCCA
hsa-miR-3191 CUCUCUGGCCGUCUACCUUCCA UGGGGACGUAGCUGGCCAGACAG
hsa-miR-3192 UCUGGGAGGUUGUAGCAGUGGAA CUCUGAUCGCCCUCUCAGCUC
hsa-miR-3193 UCCUGCGUAGGAUCUGAGGAGU UCCUCAGAUCCUACGCAGGAUU
hsa-miR-3194 AGCUCUGCUGCUCACUGGCAGU GGCCAGCCACCAGGAGGGCUG
hsa-miR-3195 CGCGCCGGGCCCGGGUU CCCGGGCCCGGCGCGUU
hsa-miR-3196 CGGGGCGGCAGGGGCCUC GGCCCCUGCCGCCCCGUU
hsa-miR-3197 GGAGGCGCAGGCUCGGAAAGGCG CCUUUCCGAGCCUGCGCCUCCUU
hsa-miR-3198 GUGGAGUCCUGGGGAAUGGAGA UCCAUUCCCCAGGACUCCACUU
hsa-miR-3199 AGGGACUGCCUUAGGAGAAAGUU CUUUCUCCUAAGGCAGUCCCUUU
hsa-miR-32 CAAUUUAGUGUGUGUGAUAUUU UAUUGCACAUUACUAAGUUGCA
hsa-miR-3200 CACCUUGCGCUACUCAGGUCUG AAUCUGAGAAGGCGCACAAGGU
hsa-miR-3201 GGGAUAUGAAGAAAAAU UUUUCUUCAUAUCCCUU
hsa-miR-3202 UGGAAGGGAGAAGAGCUUUAAU UAAAGCUCUUCUCCCUUCCAUU
hsa-miR-320a AAAAGCUGGGUUGAGAGGGCGA GCCCUCUCAACCCAGCUUUUUU
hsa-miR-320b AAAAGCUGGGUUGAGAGGGCAA GCCCUCUCAACCCAGCUUUUUU
hsa-miR-320c AAAAGCUGGGUUGAGAGGGU CCUCUCAACCCAGCUUUUUU
hsa-miR-320d AAAAGCUGGGUUGAGAGGA CUCUCAACCCAGCUUUUUU
hsa-miR-320e AAAGCUGGGUUGAGAAGG UUCUCAACCCAGCUUUUU
hsa-miR-323a AGGUGGUCCGUGGCGCGUUCGC CACAUUACACGGUCGACCUCU
hsa-miR-323b AGGUUGUCCGUGGUGAGUUCGCA CCCAAUACACGGUCGACCUCUU
hsa-miR-324 CGCAUCCCCUAGGGCAUUGGUGU ACUGCCCCAGGUGCUGCUGG
hsa-miR-325 CCUAGUAGGUGUCCAGUAAGUGU ACUUACUGGACACCUACUAGGUU
hsa-miR-326 CCUCUGGGCCCUUCCUCCAG GGAGGAAGGGCCCAGAGGUU
hsa-miR-328 CUGGCCCUCUCUGCCCUUCCGU GGGGGGGCAGGAGGGGCUCAGGG
hsa-miR-329 AACACACCUGGUUAACCUCUUU GAGGUUUUCUGGGUUUCUGUUUC
hsa-miR-330 GCAAAGCACACGGCCUGCAGAGA UCUCUGGGCCUGUGUCUUAGGC
hsa-miR-331 CUAGGUAUGGUCCCAGGGAUCC GCCCCUGGGCCUAUCCUAGAA
hsa-miR-335 UCAAGAGCAAUAACGAAAAAUGU UUUUUCAUUAUUGCUCCUGACC
hsa-miR-337 GAACGGCUUCAUACAGGAGUU CUCCUAUAUGAUGCCUUUCUUC
hsa-miR-338 UCCAGCAUCAGUGAUUUUGUUG AACAAUAUCCUGGUGCUGAGUG
hsa-miR-339 UGAGCGCCUCGACGACAGAGCCG UCCCUGUCCUCCAGGAGCUCACG
hsa-miR-33a GUGCAUUGUAGUUGCAUUGCA CAAUGUUUCCACAGUGCAUCAC
hsa-miR-33b GUGCAUUGCUGUUGCAUUGC CAGUGCCUCGGCAGUGCAGCCC
hsa-miR-340 UCCGUCUCAGUUACUUUAUAGC UUAUAAAGCAAUGAGACUGAUU
hsa-miR-342 UCUCACACAGAAAUCGCACCCGU AGGGGUGCUAUCUGUGAUUGA
hsa-miR-345 GCCCUGAACGAGGGGUCUGGAG GCUGACUCCUAGUCCAGGGCUC
hsa-miR-346 UGUCUGCCCGCAUGCCUGCCUCU AGGCAGGCAUGCGGGCAGACAUU
hsa-miR-34a UGGCAGUGUCUUAGCUGGUUGU CAAUCAGCAAGUAUACUGCCCU
hsa-miR-34b UAGGCAGUGUCAUUAGCUGAUUG CAAUCACUAACUCCACUGCCAU
hsa-miR-34c AAUCACUAACCACACGGCCAGG AGGCAGUGUAGUUAGCUGAUUGC
hsa-miR-3529 AACAACAAAAUCACUAGUCUUCCA AGGUAGACUGGGAUUUGUUGUU
hsa-miR-3591 AAACACCAUUGUCACACUCCAC UUUAGUGUGAUAAUGGCGUUUGA
hsa-miR-3605 CCUCCGUGUUACCUGUCCUCUAG UGAGGAUGGAUAGCAAGGAAGCC
hsa-miR-3606 UUAGUGAAGGCUAUUUUAAUU AAAAUUUCUUUCACUACUUAG
hsa-miR-3607 ACUGUAAACGCUUUCUGAUG GCAUGUGAUGAAGCAAAUCAGU
hsa-miR-3609 CAAAGUGAUGAGUAAUACUGGCUG GCCAGUAUUACUCAUCACUUUGUU
hsa-miR-361 UCCCCCAGGUGUGAUUCUGAUUU UUAUCAGAAUCUCCAGGGGUAC
hsa-miR-3610 GAAUCGGAAAGGAGGCGCCG GCGCCUCCUUUCCGAUUCUU
hsa-miR-3611 UUGUGAAGAAAGAAAUUCUUA AGAAUUUCUUUCUUCACAAUU
hsa-miR-3612 AGGAGGCAUCUUGAGAAAUGGA CAUUUCUCAAGAUGCCUCCUUU
hsa-miR-3613 UGUUGUACUUUUUUUUUUGUUC ACAAAAAAAAAAGCCCAACCCUUC
hsa-miR-3614 CCACUUGGAUCUGAAGGCUGCCC UAGCCUUCAGAUCUUGGUGUUUU
hsa-miR-3615 UCUCUCGGCUCCUCGCGGCUC GCCGCGAGGAGCCGAGAGAUU
hsa-miR-3616 AUGAAGUGCACUCAUGAUAUGU CGAGGGCAUUUCAUGAUGCAGGC
hsa-miR-3617 CAUCAGCACCCUAUGUCCUUUCU AAAGACAUAGUUGCAAGAUGGG
hsa-miR-3618 UGUCUACAUUAAUGAAAAGAGC UCUUUUCAUUAAUGUAGACAUU
hsa-miR-3619 UCAGCAGGCAGGCUGGUGCAGC GGGACCAUCCUGCCUGCUGUGG
hsa-miR-362 AACACACCUAUUCAAGGAUUCA AAUCCUUGGAACCUAGGUGUGAGU
hsa-miR-3620 UCACCCUGCAUCCCGCACCCAG GUGGGCUGGGCUGGGCUGGGCC
hsa-miR-3621 CGCGGGUCGGGGUCUGCAGG UGCAGACCCCGACCCGCGUU
hsa-miR-3622a UCACCUGACCUCCCAUGCCUGU CAGGCACGGGAGCUCAGGUGAG
hsa-miR-3622b UCACCUGAGCUCCCGUGCCUG AGGCAUGGGAGGUCAGGUGA
hsa-miR-363 AAUUGCACGGUAUCCAUCUGUA CGGGUGGAUCACGAUGCAAUUU
hsa-miR-3646 AAAAUGAAAUGAGCCCAGCCCA GGCUGGGCUCAUUUCAUUUUUU
hsa-miR-3648 AGCCGCGGGGAUCGCCGAGGG CUCGGCGAUCCCCGCGGCUUU
hsa-miR-3649 AGGGACCUGAGUGUCUAAG UAGACACUCAGGUCCCUUU
hsa-miR-3650 AGGUGUGUCUGUAGAGUCC ACUCUACAGACACACCUUU
hsa-miR-3651 CAUAGCCCGGUCGCUGGUACAUGA AUGUACCAGCGACCGGGCUAUGUU
hsa-miR-3652 CGGCUGGAGGUGUGAGGA CUCACACCUCCAGCCGUU
hsa-miR-3653 CCUCCUGAUGAUUCUUCUUC CUAAGAAGUUGACUGAAG
hsa-miR-3654 GACUGGACAAGCUGAGGAA CCUCAGCUUGUCCAGUCUU
hsa-miR-3655 GCUUGUCGCUGCGGUGUUGCU CAACACCGCAGCGACAAGCUU
hsa-miR-3656 GGCGGGUGCGGGGGUGG ACCCCCGCACCCGCCUU
hsa-miR-3657 UGUGUCCCAUUAUUGGUGAUU UCACCAAUAAUGGGACACAUU
hsa-miR-3658 UUUAAGAAAACACCAUGGAGAU CUCCAUGGUGUUUUCUUAAAUU
hsa-miR-3659 UGAGUGUUGUCUACGAGGGCA CCCUCGUAGACAACACUCAUU
hsa-miR-365a UAAUGCCCCUAAAAAUCCUUAU AGGGACUUUUGGGGGCAGAUGUG
hsa-miR-365b UAAUGCCCCUAAAAAUCCUUAU AGGGACUUUCAGGGGCAGCUGU
hsa-miR-3660 ACUGACAGGAGAGCAUUUUGA AAAAUGCUCUCCUGUCAGUUU
hsa-miR-3661 UGACCUGGGACUCGGACAGCUG GCUGUCCGAGUCCCAGGUCAUU
hsa-miR-3662 GAAAAUGAUGAGUAGUGACUGAUG UCAGUCACUACUCAUCAUUUUCUU
hsa-miR-3663 UGAGCACCACACAGGCCGGGCGC GCUGGUCUGCGUGGUGCUCGG
hsa-miR-3664 UCUCAGGAGUAAAGACAGAGUU AACUCUGUCUUCACUCAUGAGU
hsa-miR-3665 AGCAGGUGCGGGGCGGCG CCGCCCCGCACCUGCUUU
hsa-miR-3666 CAGUGCAAGUGUAGAUGCCGA GGCAUCUACACUUGCACUGUU
hsa-miR-3667 ACCUUCCUCUCCAUGGGUCUUU AAAGACCCAUUGAGGAGAAGGU
hsa-miR-3668 AAUGUAGAGAUUGAUCAAAAU UUUGAUCAAUCUCUACAUUUU
hsa-miR-367 AAUUGCACUUUAGCAAUGGUGA ACUGUUGCUAAUAUGCAACUCU
hsa-miR-3670 AGAGCUCACAGCUGUCCUUCUCUA GAGAAGGACAGCUGUGAGCUCUUU
hsa-miR-3671 AUCAAAUAAGGACUAGUCUGCA CAGACUAGUCCUUAUUUGAUUU
hsa-miR-3672 AUGAGACUCAUGUAAAACAUCUU GAUGUUUUACAUGAGUCUCAUUU
hsa-miR-3674 AUUGUAGAACCUAAGAUUGGCC CCAAUCUUAGGUUCUACAAUUU
hsa-miR-3675 CAUCUCUAAGGAACUCCCCCAA UAUGGGGCUUCUGUAGAGAUUUC
hsa-miR-3677 CAGUGGCCAGAGCCCUGCAGUG CUCGUGGGCUCUGGCCACGGCC
hsa-miR-3678 CUGCAGAGUUUGUACGGACCGG UCCGUACAAACUCUGCUGUG
hsa-miR-3679 CUUCCCCCCAGUAAUCUUCAUC UGAGGAUAUGGCAGGGAAGGGGA
hsa-miR-3680 GACUCACUCACAGGAUUGUGCA UUUUGCAUGACCCUGGGAGUAGG
hsa-miR-3681 UAGUGGAUGAUGCACUCUGUGC ACACAGUGCUUCAUCCACUACU
hsa-miR-3682 CUACUUCUACCUGUGUUAUCAU UGAUGAUACAGGUGGAGGUAG
hsa-miR-3683 UGCGACAUUGGAAGUAGUAUCA AUACUACUUCCAAUGUCGCAUU
hsa-miR-3684 UUAGACCUAGUACACGUCCUU GGACGUGUACUAGGUCUAAUU
hsa-miR-3685 UUUCCUACCCUACCUGAAGACU UCUUCAGGUAGGGUAGGAAAUU
hsa-miR-3686 AUCUGUAAGAGAAAGUAAAUGA AUUUACUUUCUCUUACAGAUUU
hsa-miR-3687 CCCGGACAGGCGUUCGUGCGACGU GUCGCACGAACGCCUGUCCGGGUU
hsa-miR-3688 UAUGGAAAGACUUUGCCACUCU AGUGGCAAAGUCUUUCCAUAU
hsa-miR-3689a CUGGGAGGUGUGAUAUCGUGGU UGUGAUAUCAUGGUUCCUGGGA
hsa-miR-3689b CUGGGAGGUGUGAUAUUGUGGU UGUGAUAUCAUGGUUCCUGGGA
hsa-miR-3689c CUGGGAGGUGUGAUAUUGUGGU CACAAUAUCACACCUCCCAGUU
hsa-miR-3689d GGGAGGUGUGAUCUCACACUCG AGUGUGAGAUCACACCUCCCUU
hsa-miR-3689e UGUGAUAUCAUGGUUCCUGGGA CCAGGAACCAUGAUAUCACAUU
hsa-miR-3689f UGUGAUAUCGUGCUUCCUGGGA CCAGGAAGCACGAUAUCACAUU
hsa-miR-369 AAUAAUACAUGGUUGAUCUUU AGAUCGACCGUGUUAUAUUCGC
hsa-miR-3690 ACCUGGACCCAGCGUAGACAAAG UUGUCUACGCUGGGUCCAGGUUU
hsa-miR-3691 AGUGGAUGAUGGAGACUCGGUAC ACCAAGUCUGCGUCAUCCUCUC
hsa-miR-3692 GUUCCACACUGACACUGCAGAAGU CCUGCUGGUCAGGAGUGGAUACUG
hsa-miR-370 GCCUGCUGGGGUGGAACCUGGU CAGGUCACGUCUCUGCAGUUAC
hsa-miR-3713 GGUAUCCGUUUGGGGAUGGU CAUCCCCAAACGGAUACCUU
hsa-miR-3714 GAAGGCAGCAGUGCUCCCCUGU AGGGGAGCACUGCUGCCUUCUU
hsa-miR-371a ACUCAAACUGUGGGGGCACU AAGUGCCGCCAUCUUUUGAGUGU
hsa-miR-371b ACUCAAAAGAUGGCGGCACUUU AAGUGCCCCCACAGUUUGAGUGC
hsa-miR-372 CCUCAAAUGUGGAGCACUAUUCU AAAGUGCUGCGACAUUUGAGCGU
hsa-miR-373 GAAGUGCUUCGAUUUUGGGGUGU ACUCAAAAUGGGGGCGCUUUCC
hsa-miR-374a UUAUAAUACAACCUGAUAAGUG CUUAUCAGAUUGUAUUGUAAUU
hsa-miR-374b CUUAGCAGGUUGUAUUAUCAUU AUAUAAUACAACCUGCUAAGUG
hsa-miR-374c CACUUAGCAGGUUGUAUUAUAU AUAAUACAACCUGCUAAGUGCU
hsa-miR-375 UUUGUUCGUUCGGCUCGCGUGA ACGCGAGCCGAACGAACAAAUU
hsa-miR-376a-1 AUCAUAGAGGAAAAUCCACGU GUAGAUUCUCCUUCUAUGAGUA
hsa-miR-376a-2 AUCAUAGAGGAAAAUCCACGU GGUAGAUUUUCCUUCUAUGGU
hsa-miR-376b CGUGGAUAUUCCUUCUAUGUUU AUCAUAGAGGAAAAUCCAUGUU
hsa-miR-376c GGUGGAUAUUCCUUCUAUGUU AACAUAGAGGAAAUUCCACGU
hsa-miR-377 AGAGGUUGCCCUUGGUGAAUUC AUCACACAAAGGCAACUUUUGU
hsa-miR-378a CUCCUGACUCCAGGUCCUGUGU ACUGGACUUGGAGUCAGAAGGC
hsa-miR-378b ACUGGACUUGGAGGCAGAA CUGCCUCCAAGUCCAGUUU
hsa-miR-378c ACUGGACUUGGAGUCAGAAGAGUGG ACUCUUCUGACUCCAAGUCCAGUUU
hsa-miR-378d ACUGGACUUGGAGUCAGAAA UCUGACUCCAAGUCCAGUUU
hsa-miR-378e ACUGGACUUGGAGUCAGGA CUGACUCCAAGUCCAGUUU
hsa-miR-378f ACUGGACUUGGAGCCAGAAG UCUGGCUCCAAGUCCAGUUU
hsa-miR-378g ACUGGGCUUGGAGUCAGAAG UCUGACUCCAAGCCCAGUUU
hsa-miR-378h ACUGGACUUGGUGUCAGAUGG AUCUGACACCAAGUCCAGUUU
hsa-miR-378i ACUGGACUAGGAGUCAGAAGG UUCUGACUCCUAGUCCAGUUU
hsa-miR-378j ACUGGAUUUGGAGCCAGAA CUGGCUCCAAAUCCAGUUU
hsa-miR-379 UGGUAGACUAUGGAACGUAGG UAUGUAACAUGGUCCACUAACU
hsa-miR-380 UGGUUGACCAUAGAACAUGCGC UAUGUAAUAUGGUCCACAUCUU
hsa-miR-381 AGCGAGGUUGCCCUUUGUAUAU UAUACAAGGGCAAGCUCUCUGU
hsa-miR-382 AAUCAUUCACGGACAACACUU GAAGUUGUUCGUGGUGGAUUCG
hsa-miR-383 ACAGCACUGCCUGGUCAGA AGAUCAGAAGGUGAUUGUGGCU
hsa-miR-384 AUUCCUAGAAAUUGUUCAUA UGAACAAUUUCUAGGAAUUU
hsa-miR-3907 AGGUGCUCCAGGCUGGCUCACA UGAGCCAGCCUGGAGCACCUUU
hsa-miR-3908 GAGCAAUGUAGGUAGACUGUUU ACAGUCUACCUACAUUGCUCUU
hsa-miR-3909 UGUCCUCUAGGGCCUGCAGUCU ACUGCAGGCCCUAGAGGACAUU
hsa-miR-3910 AAAGGCAUAAAACCAAGACA UCUUGGUUUUAUGCCUUUUU
hsa-miR-3911 UGUGUGGAUCCUGGAGGAGGCA CCUCCUCCAGGAUCCACACAUU
hsa-miR-3912 UAACGCAUAAUAUGGACAUGU AUGUCCAUAUUAUGGGUUAGU
hsa-miR-3913 UUUGGGACUGAUCUUGAUGUCU AGACAUCAAGAUCAGUCCCAAA
hsa-miR-3914 AAGGAACCAGAAAAUGAGAAGU UUCUCAUUUUCUGGUUCCUUUU
hsa-miR-3915 UUGAGGAAAAGAUGGUCUUAUU UAAGACCAUCUUUUCCUCAAUU
hsa-miR-3916 AAGAGGAAGAAAUGGCUGGUUCUCAG GAGAACCAGCCAUUUCUUCCUCUUUU
hsa-miR-3917 GCUCGGACUGAGCAGGUGGG CACCUGCUCAGUCCGAGCUU
hsa-miR-3918 ACAGGGCCGCAGAUGGAGACU UCUCCAUCUGCGGCCCUGUUU
hsa-miR-3919 GCAGAGAACAAAGGACUCAGU UGAGUCCUUUGUUCUCUGCUU
hsa-miR-3920 ACUGAUUAUCUUAACUCUCUGA AGAGAGUUAAGAUAAUCAGUUU
hsa-miR-3921 UCUCUGAGUACCAUAUGCCUUGU AAGGCAUAUGGUACUCAGAGAUU
hsa-miR-3922 UCUGGCCUUGACUUGACUCUUU UCAAGGCCAGAGGUCCCACAGCA
hsa-miR-3923 AACUAGUAAUGUUGGAUUAGGG CUAAUCCAACAUUACUAGUUUU
hsa-miR-3924 AUAUGUAUAUGUGACUGCUACU UAGCAGUCACAUAUACAUAUUU
hsa-miR-3925 AAGAGAACUGAAAGUGGAGCCU ACUCCAGUUUUAGUUCUCUUG
hsa-miR-3926 UGGCCAAAAAGCAGGCAGAGA UCUGCCUGCUUUUUGGCCAUU
hsa-miR-3927 CAGGUAGAUAUUUGAUAGGCAU GCCUAUCACAUAUCUGCCUGU
hsa-miR-3928 UGAAGCUCUAAGGUUCCGCCUGC GGAGGAACCUUGGAGCUUCGGC
hsa-miR-3929 GAGGCUGAUGUGAGUAGACCACU UGGUCUACUCACAUCAGCCUCUU
hsa-miR-3934 UCAGGUGUGGAAACUGAGGCAG UGCUCAGGUUGCACAGCUGGGA
hsa-miR-3935 UGUAGAUACGAGCACCAGCCAC GGCUGGUGCUCGUAUCUACAUU
hsa-miR-3936 UAAGGGGUGUAUGGCAGAUGCA CAUCUGCCAUACACCCCUUAUU
hsa-miR-3937 ACAGGCGGCUGUAGCAAUGGGGG CCCAUUGCUACAGCCGCCUGUUU
hsa-miR-3938 AAUUCCCUUGUAGAUAACCCGG GGGUUAUCUACAAGGGAAUUUU
hsa-miR-3939 UACGCGCAGACCACAGGAUGUC CAUCCUGUGGUCUGCGCGUAUU
hsa-miR-3940 GUGGGUUGGGGCGGGCUCUG CAGCCCGGAUCCCAGCCCACUU
hsa-miR-3941 UUACACACAACUGAGGAUCAUA UGAUCCUCAGUUGUGUGUAAUU
hsa-miR-3942 AAGCAAUACUGUUACCUGAAAU UUUCAGAUAACAGUAUUACAU
hsa-miR-3943 UAGCCCCCAGGCUUCACUUGGCG CCAAGUGAAGCCUGGGGGCUAUU
hsa-miR-3944 UUCGGGCUGGCCUGCUGCUCCGG UGUGCAGCAGGCCAACCGAGA
hsa-miR-3945 AGGGCAUAGGAGAGGGUUGAUAU AUCAACCCUCUCCUAUGCCCUUU
hsa-miR-3960 GGCGGCGGCGGAGGCGGGGG CCCGCCUCCGCCGCCGCCUU
hsa-miR-3972 CUGCCAGCCCCGUUCCAGGGCA CCCUGGAACGGGGCUGGCAGUU
hsa-miR-3973 ACAAAGUACAGCAUUAGCCUUAG AAGGCUAAUGCUGUACUUUGUUU
hsa-miR-3974 AAAGGUCAUUGUAAGGUUAAUGC AUUAACCUUACAAUGACCUUUUU
hsa-miR-3975 UGAGGCUAAUGCACUACUUCAC GAAGUAGUGCAUUAGCCUCAUU
hsa-miR-3976 UAUAGAGAGCAGGAAGAUUAAUGU AUUAAUCUUCCUGCUCUCUAUAUU
hsa-miR-3977 GUGCUUCAUCGUAAUUAACCUUA AGGUUAAUUACGAUGAAGCACUU
hsa-miR-3978 GUGGAAAGCAUGCAUCCAGGGUGU ACCCUGGAUGCAUGCUUUCCACUU
hsa-miR-409 GAAUGUUGCUCGGUGAACCCCU AGGUUACCCGAGCAACUUUGCAU
hsa-miR-410 AGGUUGUCUGUGAUGAGUUCG AAUAUAACACAGAUGGCCUGU
hsa-miR-411 UAUGUAACACGGUCCACUAACC UAGUAGACCGUAUAGCGUACG
hsa-miR-412 UGGUCGACCAGUUGGAAAGUAAU ACUUCACCUGGUCCACUAGCCGU
hsa-miR-421 AUCAACAGACAUUAAUUGGGCGC GCCCAAUUAAUGUCUGUUGAUUU
hsa-miR-422a ACUGGACUUAGGGUCAGAAGGC CUUCUGACCCUAAGUCCAGUUU
hsa-miR-423 UGAGGGGCAGAGAGCGAGACUUU AGCUCGGUCUGAGGCCCCUCAGU
hsa-miR-424 CAGCAGCAAUUCAUGUUUUGAA CAAAACGUGAGGCGCUGCUAU
hsa-miR-425 AUCGGGAAUGUCGUGUCCGCCC AAUGACACGAUCACUCCCGUUGA
hsa-miR-4251 CCUGAGAAAAGGGCCAA GGCCCUUUUCUCAGGUU
hsa-miR-4252 GGCCACUGAGUCAGCACCA GUGCUGACUCAGUGGCCUU
hsa-miR-4253 AGGGCAUGUCCAGGGGGU CCCCUGGACAUGCCCUUU
hsa-miR-4254 GCCUGGAGCUACUCCACCAUCUC GAUGGUGGAGUAGCUCCAGGCUU
hsa-miR-4255 CAGUGUUCAGAGAUGGA CAUCUCUGAACACUGUU
hsa-miR-4256 AUCUGACCUGAUGAAGGU CUUCAUCAGGUCAGAUUU
hsa-miR-4257 CCAGAGGUGGGGACUGAG CAGUCCCCACCUCUGGUU
hsa-miR-4258 CCCCGCCACCGCCUUGG AAGGCGGUGGCGGGGUU
hsa-miR-4259 CAGUUGGGUCUAGGGGUCAGGA CUGACCCCUAGACCCAACUGUU
hsa-miR-4260 CUUGGGGCAUGGAGUCCCA GGACUCCAUGCCCCAAGUU
hsa-miR-4261 AGGAAACAGGGACCCA GGUCCCUGUUUCCUUU
hsa-miR-4262 GACAUUCAGACUACCUG GGUAGUCUGAAUGUCUU
hsa-miR-4263 AUUCUAAGUGCCUUGGCC CCAAGGCACUUAGAAUUU
hsa-miR-4264 ACUCAGUCAUGGUCAUU UGACCAUGACUGAGUUU
hsa-miR-4265 CUGUGGGCUCAGCUCUGGG CAGAGCUGAGCCCACAGUU
hsa-miR-4266 CUAGGAGGCCUUGGCC CCAAGGCCUCCUAGUU
hsa-miR-4267 UCCAGCUCGGUGGCAC GCCACCGAGCUGGAUU
hsa-miR-4268 GGCUCCUCCUCUCAGGAUGUG CAUCCUGAGAGGAGGAGCCUU
hsa-miR-4269 GCAGGCACAGACAGCCCUGGC CAGGGCUGUCUGUGCCUGCUU
hsa-miR-4270 UCAGGGAGUCAGGGGAGGGC CCUCCCCUGACUCCCUGAUU
hsa-miR-4271 GGGGGAAGAAAAGGUGGGG CCACCUUUUCUUCCCCCUU
hsa-miR-4272 CAUUCAACUAGUGAUUGU AAUCACUAGUUGAAUGUU
hsa-miR-4273 GUGUUCUCUGAUGGACAG GUCCAUCAGAGAACACUU
hsa-miR-4274 CAGCAGUCCCUCCCCCUG GGGGGAGGGACUGCUGUU
hsa-miR-4275 CCAAUUACCACUUCUUU AGAAGUGGUAAUUGGUU
hsa-miR-4276 CUCAGUGACUCAUGUGC ACAUGAGUCACUGAGUU
hsa-miR-4277 GCAGUUCUGAGCACAGUACAC GUACUGUGCUCAGAACUGCUU
hsa-miR-4278 CUAGGGGGUUUGCCCUUG AGGGCAAACCCCCUAGUU
hsa-miR-4279 CUCUCCUCCCGGCUUC AGCCGGGAGGAGAGUU
hsa-miR-4280 GAGUGUAGUUCUGAGCAGAGC UCUGCUCAGAACUACACUCUU
hsa-miR-4281 GGGUCCCGGGGAGGGGGG CCCCUCCCCGGGACCCUU
hsa-miR-4282 UAAAAUUUGCAUCCAGGA CUGGAUGCAAAUUUUAUU
hsa-miR-4283 UGGGGCUCAGCGAGUUU ACUCGCUGAGCCCCAUU
hsa-miR-4284 GGGCUCACAUCACCCCAU GGGGUGAUGUGAGCCCUU
hsa-miR-4285 GCGGCGAGUCCGACUCAU GAGUCGGACUCGCCGCUU
hsa-miR-4286 ACCCCACUCCUGGUACC UACCAGGAGUGGGGUUU
hsa-miR-4287 UCUCCCUUGAGGGCACUUU AGUGCCCUCAAGGGAGAUU
hsa-miR-4288 UUGUCUGCUGAGUUUCC AAACUCAGCAGACAAUU
hsa-miR-4289 GCAUUGUGCAGGGCUAUCA AUAGCCCUGCACAAUGCUU
hsa-miR-429 UAAUACUGUCUGGUAAAACCGU GGUUUUACCAGACAGUAUUAUU
hsa-miR-4290 UGCCCUCCUUUCUUCCCUC GGGAAGAAAGGAGGGCAUU
hsa-miR-4291 UUCAGCAGGAACAGCU CUGUUCCUGCUGAAUU
hsa-miR-4292 CCCCUGGGCCGGCCUUGG AAGGCCGGCCCAGGGGUU
hsa-miR-4293 CAGCCUGACAGGAACAG GUUCCUGUCAGGCUGUU
hsa-miR-4294 GGGAGUCUACAGCAGGG CUGCUGUAGACUCCCUU
hsa-miR-4295 CAGUGCAAUGUUUUCCUU GGAAAACAUUGCACUGUU
hsa-miR-4296 AUGUGGGCUCAGGCUCA AGCCUGAGCCCACAUUU
hsa-miR-4297 UGCCUUCCUGUCUGUG CAGACAGGAAGGCAUU
hsa-miR-4298 CUGGGACAGGAGGAGGAGGCAG GCCUCCUCCUCCUGUCCCAGUU
hsa-miR-4299 GCUGGUGACAUGAGAGGC CUCUCAUGUCACCAGCUU
hsa-miR-4300 UGGGAGCUGGACUACUUC AGUAGUCCAGCUCCCAUU
hsa-miR-4301 UCCCACUACUUCACUUGUGA ACAAGUGAAGUAGUGGGAUU
hsa-miR-4302 CCAGUGUGGCUCAGCGAG CGCUGAGCCACACUGGUU
hsa-miR-4303 UUCUGAGCUGAGGACAG GUCCUCAGCUCAGAAUU
hsa-miR-4304 CCGGCAUGUCCAGGGCA CCCUGGACAUGCCGGUU
hsa-miR-4305 CCUAGACACCUCCAGUUC ACUGGAGGUGUCUAGGUU
hsa-miR-4306 UGGAGAGAAAGGCAGUA CUGCCUUUCUCUCCAUU
hsa-miR-4307 AAUGUUUUUUCCUGUUUCC AAACAGGAAAAAACAUUUU
hsa-miR-4308 UCCCUGGAGUUUCUUCUU GAAGAAACUCCAGGGAUU
hsa-miR-4309 CUGGAGUCUAGGAUUCCA GAAUCCUAGACUCCAGUU
hsa-miR-431 UGUCUUGCAGGCCGUCAUGCA CAGGUCGUCUUGCAGGGCUUCU
hsa-miR-4310 GCAGCAUUCAUGUCCC GACAUGAAUGCUGCUU
hsa-miR-4311 GAAAGAGAGCUGAGUGUG CACUCAGCUCUCUUUCUU
hsa-miR-4312 GGCCUUGUUCCUGUCCCCA GGGACAGGAACAAGGCCUU
hsa-miR-4313 AGCCCCCUGGCCCCAAACCC GUUUGGGGCCAGGGGGCUUU
hsa-miR-4314 CUCUGGGAAAUGGGACAG GUCCCAUUUCCCAGAGUU
hsa-miR-4315 CCGCUUUCUGAGCUGGAC CCAGCUCAGAAAGCGGUU
hsa-miR-4316 GGUGAGGCUAGCUGGUG CCAGCUAGCCUCACCUU
hsa-miR-4317 ACAUUGCCAGGGAGUUU ACUCCCUGGCAAUGUUU
hsa-miR-4318 CACUGUGGGUACAUGCU CAUGUACCCACAGUGUU
hsa-miR-4319 UCCCUGAGCAAAGCCAC GGCUUUGCUCAGGGAUU
hsa-miR-432 UCUUGGAGUAGGUCAUUGGGUGG CUGGAUGGCUCCUCCAUGUCU
hsa-miR-4320 GGGAUUCUGUAGCUUCCU GAAGCUACAGAAUCCCUU
hsa-miR-4321 UUAGCGGUGGACCGCCCUGCG CAGGGCGGUCCACCGCUAAUU
hsa-miR-4322 CUGUGGGCUCAGCGCGUGGGG CCACGCGCUGAGCCCACAGUU
hsa-miR-4323 CAGCCCCACAGCCUCAGA UGAGGCUGUGGGGCUGUU
hsa-miR-4324 CCCUGAGACCCUAACCUUAA AAGGUUAGGGUCUCAGGGUU
hsa-miR-4325 UUGCACUUGUCUCAGUGA ACUGAGACAAGUGCAAUU
hsa-miR-4326 UGUUCCUCUGUCUCCCAGAC CUGGGAGACAGAGGAACAUU
hsa-miR-4327 GGCUUGCAUGGGGGACUGG AGUCCCCCAUGCAAGCCUU
hsa-miR-4328 CCAGUUUUCCCAGGAUU UCCUGGGAAAACUGGUU
hsa-miR-4329 CCUGAGACCCUAGUUCCAC GGAACUAGGGUCUCAGGUU
hsa-miR-433 UACGGUGAGCCUGUCAUUAUUC AUCAUGAUGGGCUCCUCGGUGU
hsa-miR-4330 CCUCAGAUCAGAGCCUUGC AAGGCUCUGAUCUGAGGUU
hsa-miR-4417 GGUGGGCUUCCCGGAGGG CUCCGGGAAGCCCACCUU
hsa-miR-4418 CACUGCAGGACUCAGCAG GCUGAGUCCUGCAGUGUU
hsa-miR-4419a UGAGGGAGGAGACUGCA CAGUCUCCUCCCUCAUU
hsa-miR-4419b GAGGCUGAAGGAAGAUGG AUCUUCCUUCAGCCUCUU
hsa-miR-4420 GUCACUGAUGUCUGUAGCUGAG CAGCUACAGACAUCAGUGACUU
hsa-miR-4421 ACCUGUCUGUGGAAAGGAGCUA GCUCCUUUCCACAGACAGGUUU
hsa-miR-4422 AAAAGCAUCAGGAAGUACCCA GGUACUUCCUGAUGCUUUUUU
hsa-miR-4423 AGUUGCCUUUUUGUUCCCAUGC AUAGGCACCAAAAAGCAACAA
hsa-miR-4424 AGAGUUAACUCAAAAUGGACUA GUCCAUUUUGAGUUAACUCUUU
hsa-miR-4425 UGUUGGGAUUCAGCAGGACCAU GGUCCUGCUGAAUCCCAACAUU
hsa-miR-4426 GAAGAUGGACGUACUUU AGUACGUCCAUCUUCUU
hsa-miR-4427 UCUGAAUAGAGUCUGAAGAGU UCUUCAGACUCUAUUCAGAUU
hsa-miR-4428 CAAGGAGACGGGAACAUGGAGC UCCAUGUUCCCGUCUCCUUGUU
hsa-miR-4429 AAAAGCUGGGCUGAGAGGCG CCUCUCAGCCCAGCUUUUUU
hsa-miR-4430 AGGCUGGAGUGAGCGGAG CCGCUCACUCCAGCCUUU
hsa-miR-4431 GCGACUCUGAAAACUAGAAGGU CUUCUAGUUUUCAGAGUCGCUU
hsa-miR-4432 AAAGACUCUGCAAGAUGCCU GCAUCUUGCAGAGUCUUUUU
hsa-miR-4433a ACAGGAGUGGGGGUGGGACAU CGUCCCACCCCCCACUCCUGU
hsa-miR-4433b CAGGAGUGGGGGGUGGGACGU AUGUCCCACCCCCACUCCUGU
hsa-miR-4434 AGGAGAAGUAAAGUAGAA CUACUUUACUUCUCCUUU
hsa-miR-4435 AUGGCCAGAGCUCACACAGAGG UCUGUGUGAGCUCUGGCCAUUU
hsa-miR-4436a GCAGGACAGGCAGAAGUGGAU CCACUUCUGCCUGUCCUGCUU
hsa-miR-4436b GUCCACUUCUGCCUGCCCUGCC CAGGGCAGGAAGAAGUGGACAA
hsa-miR-4437 UGGGCUCAGGGUACAAAGGUU CCUUUGUACCCUGAGCCCAUU
hsa-miR-4438 CACAGGCUUAGAAAAGACAGU UGUCUUUUCUAAGCCUGUGUU
hsa-miR-4439 GUGACUGAUACCUUGGAGGCAU GCCUCCAAGGUAUCAGUCACUU
hsa-miR-4440 UGUCGUGGGGCUUGCUGGCUUG AGCCAGCAAGCCCCACGACAUU
hsa-miR-4441 ACAGGGAGGAGAUUGUA CAAUCUCCUCCCUGUUU
hsa-miR-4442 GCCGGACAAGAGGGAGG UCCCUCUUGUCCGGCUU
hsa-miR-4443 UUGGAGGCGUGGGUUUU AACCCACGCCUCCAAUU
hsa-miR-4444 CUCGAGUUGGAAGAGGCG CCUCUUCCAACUCGAGUU
hsa-miR-4445 AGAUUGUUUCUUUUGCCGUGCA CACGGCAAAAGAAACAAUCCA
hsa-miR-4446 AUUUCCCUGCCAUUCCCUUGGC CAGGGCUGGCAGUGACAUGGGU
hsa-miR-4447 GGUGGGGGCUGUUGUUU ACAACAGCCCCCACCUU
hsa-miR-4448 GGCUCCUUGGUCUAGGGGUA CCCCUAGACCAAGGAGCCUU
hsa-miR-4449 CGUCCCGGGGCUGCGCGAGGCA CCUCGCGCAGCCCCGGGACGUU
hsa-miR-4450 UGGGGAUUUGGAGAAGUGGUGA ACCACUUCUCCAAAUCCCCAUU
hsa-miR-4451 UGGUAGAGCUGAGGACA UCCUCAGCUCUACCAUU
hsa-miR-4452 UUGAAUUCUUGGCCUUAAGUGAU CACUUAAGGCCAAGAAUUCAAUU
hsa-miR-4453 GAGCUUGGUCUGUAGCGGUU CCGCUACAGACCAAGCUCUU
hsa-miR-4454 GGAUCCGAGUCACGGCACCA GUGCCGUGACUCGGAUCCUU
hsa-miR-4455 AGGGUGUGUGUGUUUUU AAACACACACACCCUUU
hsa-miR-4456 CCUGGUGGCUUCCUUUU AAGGAAGCCACCAGGUU
hsa-miR-4457 UCACAAGGUAUUGACUGGCGUA CGCCAGUCAAUACCUUGUGAUU
hsa-miR-4458 AGAGGUAGGUGUGGAAGAA CUUCCACACCUACCUCUUU
hsa-miR-4459 CCAGGAGGCGGAGGAGGUGGAG CCACCUCCUCCGCCUCCUGGUU
hsa-miR-4460 AUAGUGGUUGUGAAUUUACCUU GGUAAAUUCACAACCACUAUUU
hsa-miR-4461 GAUUGAGACUAGUAGGGCUAGGC CUAGCCCUACUAGUCUCAAUCUU
hsa-miR-4462 UGACACGGAGGGUGGCUUGGGAA CCCAAGCCACCCUCCGUGUCAUU
hsa-miR-4463 GAGACUGGGGUGGGGCC CCCCACCCCAGUCUCUU
hsa-miR-4464 AAGGUUUGGAUAGAUGCAAUA UUGCAUCUAUCCAAACCUUUU
hsa-miR-4465 CUCAAGUAGUCUGACCAGGGGA CCCUGGUCAGACUACUUGAGUU
hsa-miR-4466 GGGUGCGGGCCGGCGGGG CCGCCGGCCCGCACCCUU
hsa-miR-4467 UGGCGGCGGUAGUUAUGGGCUU GCCCAUAACUACCGCCGCCAUU
hsa-miR-4468 AGAGCAGAAGGAUGAGAU CUCAUCCUUCUGCUCUUU
hsa-miR-4469 GCUCCCUCUAGGGUCGCUCGGA CGAGCGACCCUAGAGGGAGCUU
hsa-miR-4470 UGGCAAACGUGGAAGCCGAGA UCGGCUUCCACGUUUGCCAUU
hsa-miR-4471 UGGGAACUUAGUAGAGGUUUAA AAACCUCUACUAAGUUCCCAUU
hsa-miR-4472 GGUGGGGGGUGUUGUUUU AACAACACCCCCCACCUU
hsa-miR-4473 CUAGUGCUCUCCGUUACAAGUA CUUGUAACGGAGAGCACUAGUU
hsa-miR-4474 UUGUGGCUGGUCAUGAGGCUAA UUAGUCUCAUGAUCAGACACA
hsa-miR-4475 CAAGGGACCAAGCAUUCAUUAU AAUGAAUGCUUGGUCCCUUGUU
hsa-miR-4476 CAGGAAGGAUUUAGGGACAGGC CUGUCCCUAAAUCCUUCCUGUU
hsa-miR-4477a CUAUUAAGGACAUUUGUGAUUC AUCACAAAUGUCCUUAAUAGUU
hsa-miR-4477b AUUAAGGACAUUUGUGAUUGAU CAAUCACAAAUGUCCUUAAUUU
hsa-miR-4478 GAGGCUGAGCUGAGGAG CCUCAGCUCAGCCUCUU
hsa-miR-4479 CGCGCGGCCGUGCUCGGAGCAG GCUCCGAGCACGGCCGCGCGUU
hsa-miR-448 UUGCAUAUGUAGGAUGUCCCAU GGGACAUCCUACAUAUGCAAUU
hsa-miR-4480 AGCCAAGUGGAAGUUACUUUA AAGUAACUUCCACUUGGCUUU
hsa-miR-4481 GGAGUGGGCUGGUGGUU CCACCAGCCCACUCCUU
hsa-miR-4482 UUUCUAUUUCUCAGUGGGGCUC AACCCAGUGGGCUAUGGAAAUG
hsa-miR-4483 GGGGUGGUCUGUUGUUG ACAACAGACCACCCCUU
hsa-miR-4484 AAAAGGCGGGAGAAGCCCCA GGGCUUCUCCCGCCUUUUUU
hsa-miR-4485 UAACGGCCGCGGUACCCUAA ACCGCCUGCCCAGUGA
hsa-miR-4486 GCUGGGCGAGGCUGGCA CCAGCCUCGCCCAGCUU
hsa-miR-4487 AGAGCUGGCUGAAGGGCAG GCCCUUCAGCCAGCUCUUU
hsa-miR-4488 AGGGGGCGGGCUCCGGCG CCGGAGCCCGCCCCCUUU
hsa-miR-4489 UGGGGCUAGUGAUGCAGGACG UCCUGCAUCACUAGCCCCAUU
hsa-miR-4490 UCUGGUAAGAGAUUUGGGCAUA UGCCCAAAUCUCUUACCAGAUU
hsa-miR-4491 AAUGUGGACUGGUGUGACCAAA UGGUCACACCAGUCCACAUUUU
hsa-miR-4492 GGGGCUGGGCGCGCGCC CGCGCGCCCAGCCCCUU
hsa-miR-4493 AGAAGGCCUUUCCAUCUCUGU AGAGAUGGAAAGGCCUUCUUU
hsa-miR-4494 CCAGACUGUGGCUGACCAGAGG UCUGGUCAGCCACAGUCUGGUU
hsa-miR-4495 AAUGUAAACAGGCUUUUUGCU CAAAAAGCCUGUUUACAUUUU
hsa-miR-4496 GAGGAAACUGAAGCUGAGAGGG CUCUCAGCUUCAGUUUCCUCUU
hsa-miR-4497 CUCCGGGACGGCUGGGC CCAGCCGUCCCGGAGUU
hsa-miR-4498 UGGGCUGGCAGGGCAAGUGCUG GCACUUGCCCUGCCAGCCCAUU
hsa-miR-4499 AAGACUGAGAGGAGGGA CCUCCUCUCAGUCUUUU
hsa-miR-449a UGGCAGUGUAUUGUUAGCUGGU CAGCUAACAAUACACUGCCAUU
hsa-miR-449b CAGCCACAACUACCCUGCCACU AGGCAGUGUAUUGUUAGCUGGC
hsa-miR-449c UAGGCAGUGUAUUGCUAGCGGCUGU UUGCUAGUUGCACUCCUCUCUGU
hsa-miR-4500 UGAGGUAGUAGUUUCUU GAAACUACUACCUCAUU
hsa-miR-4501 UAUGUGACCUCGGAUGAAUCA AUUCAUCCGAGGUCACAUAUU
hsa-miR-4502 GCUGAUGAUGAUGGUGCUGAAG UCAGCACCAUCAUCAUCAGCUU
hsa-miR-4503 UUUAAGCAGGAAAUAGAAUUUA AAUUCUAUUUCCUGCUUAAAUU
hsa-miR-4504 UGUGACAAUAGAGAUGAACAUG UGUUCAUCUCUAUUGUCACAUU
hsa-miR-4505 AGGCUGGGCUGGGACGGA CGUCCCAGCCCAGCCUUU
hsa-miR-4506 AAAUGGGUGGUCUGAGGCAA GCCUCAGACCACCCAUUUUU
hsa-miR-4507 CUGGGUUGGGCUGGGCUGGG CAGCCCAGCCCAACCCAGUU
hsa-miR-4508 GCGGGGCUGGGCGCGCG CGCGCCCAGCCCCGCUU
hsa-miR-4509 ACUAAAGGAUAUAGAAGGUUUU AACCUUCUAUAUCCUUUAGUUU
hsa-miR-450a-1 UUUUGCGAUGUGUUCCUAAUAU AUUGGGAACAUUUUGCAUGUAU
hsa-miR-450a-2 UUUUGCGAUGUGUUCCUAAUAU AUUGGGGACAUUUUGCAUUCAU
hsa-miR-450b UUUUGCAAUAUGUUCCUGAAUA UUGGGAUCAUUUUGCAUCCAUA
hsa-miR-4510 UGAGGGAGUAGGAUGUAUGGUU CCAUACAUCCUACUCCCUCAUU
hsa-miR-4511 GAAGAACUGUUGCAUUUGCCCU GGCAAAUGCAACAGUUCUUCUU
hsa-miR-4512 CAGGGCCUCACUGUAUCGCCCA GGCGAUACAGUGAGGCCCUGUU
hsa-miR-4513 AGACUGACGGCUGGAGGCCCAU GGGCCUCCAGCCGUCAGUCUUU
hsa-miR-4514 ACAGGCAGGAUUGGGGAA CCCCAAUCCUGCCUGUUU
hsa-miR-4515 AGGACUGGACUCCCGGCAGCCC GCUGCCGGGAGUCCAGUCCUUU
hsa-miR-4516 GGGAGAAGGGUCGGGGC CCCGACCCUUCUCCCUU
hsa-miR-4517 AAAUAUGAUGAAACUCACAGCUGAG CAGCUGUGAGUUUCAUCAUAUUUUU
hsa-miR-4518 GCUCAGGGAUGAUAACUGUGCUGAGA UCAGCACAGUUAUCAUCCCUGAGCUU
hsa-miR-4519 CAGCAGUGCGCAGGGCUG GCCCUGCGCACUGCUGUU
hsa-miR-451a AAACCGUUACCAUUACUGAGUU CUCAGUAAUGGUAACGGUUUUU
hsa-miR-451b UAGCAAGAGAACCAUUACCAUU UGGUAAUGGUUCUCUUGCUAUU
hsa-miR-452 AACUGUUUGCAGAGGAAACUGA CUCAUCUGCAAAGAAGUAAGUG
hsa-miR-4520-1 CCUGCGUGUUUUCUGUCCAA UUGGACAGAAAACACGCAGGAA
hsa-miR-4520-2 CCUGCGUGUUUUCUGUCCAA UUUGGACAGAAAACACGCAGGU
hsa-miR-4521 GCUAAGGAAGUCCUGUGCUCAG GAGCACAGGACUUCCUUAGCUU
hsa-miR-4522 UGACUCUGCCUGUAGGCCGGU CGGCCUACAGGCAGAGUCAUU
hsa-miR-4523 GACCGAGAGGGCCUCGGCUGU AGCCGAGGCCCUCUCGGUCUU
hsa-miR-4524a AUAGCAGCAUGAACCUGUCUCA UGAGACAGGCUUAUGCUGCUAU
hsa-miR-4524b AUAGCAGCAUAAGCCUGUCUC GAGACAGGUUCAUGCUGCUA
hsa-miR-4525 GGGGGGAUGUGCAUGCUGGUU CCAGCAUGCACAUCCCCCCUU
hsa-miR-4526 GCUGACAGCAGGGCUGGCCGCU CGGCCAGCCCUGCUGUCAGCUU
hsa-miR-4527 UGGUCUGCAAAGAGAUGACUGU AGUCAUCUCUUUGCAGACCAUU
hsa-miR-4528 UCAUUAUAUGUAUGAUCUGGAC CCAGAUCAUACAUAUAAUGAUU
hsa-miR-4529 AGGCCAUCAGCAGUCCAAUGAA AUUGGACUGCUGAUGGCCCGU
hsa-miR-4530 CCCAGCAGGACGGGAGCG CUCCCGUCCUGCUGGGUU
hsa-miR-4531 AUGGAGAAGGCUUCUGA AGAAGCCUUCUCCAUUU
hsa-miR-4532 CCCCGGGGAGCCCGGCG CCGGGCUCCCCGGGGUU
hsa-miR-4533 UGGAAGGAGGUUGCCGGACGCU CGUCCGGCAACCUCCUUCCAUU
hsa-miR-4534 GGAUGGAGGAGGGGUCU ACCCCUCCUCCAUCCUU
hsa-miR-4535 GUGGACCUGGCUGGGAC CCCAGCCAGGUCCACUU
hsa-miR-4536 UCGUGCAUAUAUCUACCACAU UGUGGUAGAUAUAUGCACGAU
hsa-miR-4537 UGAGCCGAGCUGAGCUUAGCUG GCUAAGCUCAGCUCGGCUCAUU
hsa-miR-4538 GAGCUUGGAUGAGCUGGGCUGA AGCCCAGCUCAUCCAAGCUCUU
hsa-miR-4539 GCUGAACUGGGCUGAGCUGGGC CCAGCUCAGCCCAGUUCAGCUU
hsa-miR-454 ACCCUAUCAAUAUUGUCUCUGC UAGUGCAAUAUUGCUUAUAGGGU
hsa-miR-4540 UUAGUCCUGCCUGUAGGUUUA AACCUACAGGCAGGACUAAUU
hsa-miR-455 GCAGUCCAUGGGCAUAUACAC UAUGUGCCUUUGGACUACAUCG
hsa-miR-4632 UGCCGCCCUCUCGCUGCUCUAG GAGGGCAGCGUGGGUGUGGCGGA
hsa-miR-4633 AUAUGCCUGGCUAGCUCCUC AGGAGCUAGCCAGGCAUAUGCA
hsa-miR-4634 CGGCGCGACCGGCCCGGGG CCGGGCCGGUCGCGCCGUU
hsa-miR-4635 UCUUGAAGUCAGAACCCGCAA GCGGGUUCUGACUUCAAGAUU
hsa-miR-4636 AACUCGUGUUCAAAGCCUUUAG AAAGGCUUUGAACACGAGUUUU
hsa-miR-4637 UACUAACUGCAGAUUCAAGUGA ACUUGAAUCUGCAGUUAGUAUU
hsa-miR-4638 CCUGGACACCGCUCAGCCGGCCG ACUCGGCUGCGGUGGACAAGU
hsa-miR-4639 UCACUCUCACCUUGCUUUGC UUGCUAAGUAGGCUGAGAUUGA
hsa-miR-4640 UGGGCCAGGGAGCAGCUGGUGGG CACCCCCUGUUUCCUGGCCCAC
hsa-miR-4641 UGCCCAUGCCAUACUUUUGCCUCA AGGCAAAAGUAUGGCAUGGGCAUU
hsa-miR-4642 AUGGCAUCGUCCCCUGGUGGCU CCACCAGGGGACGAUGCCAUUU
hsa-miR-4643 GACACAUGACCAUAAAUGCUAA AGCAUUUAUGGUCAUGUGUCUU
hsa-miR-4644 UGGAGAGAGAAAAGAGACAGAAG UCUGUCUCUUUUCUCUCUCCAUU
hsa-miR-4645 ACCAGGCAAGAAAUAUUGU AGACAGUAGUUCUUGCCUGGUU
hsa-miR-4646 AUUGUCCCUCUCCCUUCCCAG ACUGGGAAGAGGAGCUGAGGGA
hsa-miR-4647 GAAGAUGGUGCUGUGCUGAGGAA CCUCAGCACAGCACCAUCUUCUU
hsa-miR-4648 UGUGGGACUGCAAAUGGGAG CCCAUUUGCAGUCCCACAUU
hsa-miR-4649 UGGGCGAGGGGUGGGCUCUCAGAG UCUGAGGCCUGCCUCUCCCCA
hsa-miR-4650 AGGUAGAAUGAGGCCUGACAU UCAGGCCUCUUUCUACCUU
hsa-miR-4651 CGGGGUGGGUGAGGUCGGGC CCGACCUCACCCACCCCGUU
hsa-miR-4652 AGGGGACUGGUUAAUAGAACUA GUUCUGUUAACCCAUCCCCUCA
hsa-miR-4653 UCUCUGAGCAAGGCUUAACACC UGGAGUUAAGGGUUGCUUGGAGA
hsa-miR-4654 UGUGGGAUCUGGAGGCAUCUGG AGAUGCCUCCAGAUCCCACAUU
hsa-miR-4655 ACCCUCGUCAGGUCCCCGGGG CACCGGGGAUGGCAGAGGGUCG
hsa-miR-4656 UGGGCUGAGGGCAGGAGGCCUGU AGGCCUCCUGCCCUCAGCCCAUU
hsa-miR-4657 AAUGUGGAAGUGGUCUGAGGCAU GCCUCAGACCACUUCCACAUUUU
hsa-miR-4658 GUGAGUGUGGAUCCUGGAGGAAU UCCUCCAGGAUCCACACUCACUU
hsa-miR-4659a UUUCUUCUUAGACAUGGCAACG CUGCCAUGUCUAAGAAGAAAAC
hsa-miR-4659b UUUCUUCUUAGACAUGGCAGCU UUGCCAUGUCUAAGAAGAA
hsa-miR-466 AUACACAUACACGCAACACACAU GUGUGUUGCGUGUAUGUGUAUUU
hsa-miR-4660 UGCAGCUCUGGUGGAAAAUGGAG CCAUUUUCCACCAGAGCUGCAUU
hsa-miR-4661 AACUAGCUCUGUGGAUCCUGAC CAGGAUCCACAGAGCUAGUCCA
hsa-miR-4662a UUAGCCAAUUGUCCAUCUUUAG AAAGAUAGACAAUUGGCUAAAU
hsa-miR-4662b AAAGAUGGACAAUUGGCUAAAU UUAGCCAAUUGUCCAUCUUUUU
hsa-miR-4663 AGCUGAGCUCCAUGGACGUGCAGU UGCACGUCCAUGGAGCUCAGCUUU
hsa-miR-4664 CUUCCGGUCUGUGAGCCCCGUC UGGGGUGCCCACUCCGCAAGUU
hsa-miR-4665 CUCGGCCGCGGCGCGUAGCCCCCGCC CUGGGGGACGCGUGAGCGCGAGC
hsa-miR-4666a AUACAUGUCAGAUUGUAUGCC CAUACAAUCUGACAUGUAUUU
hsa-miR-4666b UUGCAUGUCAGAUUGUAAUUCCC GAAUUACAAUCUGACAUGCAAUU
hsa-miR-4667 ACUGGGGAGCAGAAGGAGAACC UCCCUCCUUCUGUCCCCACAG
hsa-miR-4668 AGGGAAAAAAAAAAGGAUUUGUC GAAAAUCCUUUUUGUUUUUCCAG
hsa-miR-4669 UGUGUCCGGGAAGUGGAGGAGG UCCUCCACUUCCCGGACACAUU
hsa-miR-4670 AAGCGACCAUGAUGUAACUUCA UGAAGUUACAUCAUGGUCGCUU
hsa-miR-4671 ACCGAAGACUGUGCGCUAAUCU UUAGUGCAUAGUCUUUGGUCU
hsa-miR-4672 UUACACAGCUGGACAGAGGCA CCUCUGUCCAGCUGUGUAAUU
hsa-miR-4673 UCCAGGCAGGAGCCGGACUGGA CAGUCCGGCUCCUGCCUGGAUU
hsa-miR-4674 CUGGGCUCGGGACGCGCGGCU CCGCGCGUCCCGAGCCCAGUU
hsa-miR-4675 GGGGCUGUGAUUGACCAGCAGG UGCUGGUCAAUCACAGCCCCUU
hsa-miR-4676 GAGCCAGUGGUGAGACAGUGA CACUGUUUCACCACUGGCUCUU
hsa-miR-4677 UUGUUCUUUGGUCUUUCAGCCA UCUGUGAGACCAAAGAACUACU
hsa-miR-4678 AAGGUAUUGUUCAGACUUAUGA AUAAGUCUGAACAAUACCUUUU
hsa-miR-4679 UCUGUGAUAGAGAUUCUUUGCU CAAAGAAUCUCUAUCACAGAUU
hsa-miR-4680 UCUGAAUUGUAAGAGUUGUUA AGAACUCUUGCAGUCUUAGAUGU
hsa-miR-4681 AACGGGAAUGCAGGCUGUAUCU AUACAGCCUGCAUUCCCGUUUU
hsa-miR-4682 UCUGAGUUCCUGGAGCCUGGUCU ACCAGGCUCCAGGAACUCAGAUU
hsa-miR-4683 UGGAGAUCCAGUGCUCGCCCGAU CGGGCGAGCACUGGAUCUCCAUU
hsa-miR-4684 CUCUCUACUGACUUGCAACAUA UGUUGCAAGUCGGUGGAGACGU
hsa-miR-4685 CCCAGGGCUUGGAGUGGGGCAAGGUU UCUCCCUUCCUGCCCUGGCUAG
hsa-miR-4686 UAUCUGCUGGGCUUUCUGGUGUU CACCAGAAAGCCCAGCAGAUAUU
hsa-miR-4687 UGGCUGUUGGAGGGGGCAGGC CAGCCCUCCUCCCGCACCCAAA
hsa-miR-4688 UAGGGGCAGCAGAGGACCUGGG CAGGUCCUCUGCUGCCCCUAUU
hsa-miR-4689 UUGAGGAGACAUGGUGGGGGCC CCCCCACCAUGUCUCCUCAAUU
hsa-miR-4690 GCAGCCCAGCUGAGGCCUCUG GAGCAGGCGAGGCUGGGCUGAA
hsa-miR-4691 GUCCUCCAGGCCAUGAGCUGCGG CCAGCCACGGACUGAGAGUGCAU
hsa-miR-4692 UCAGGCAGUGUGGGUAUCAGAU CUGAUACCCACACUGCCUGAUU
hsa-miR-4693 AUACUGUGAAUUUCACUGUCACA UGAGAGUGGAAUUCACAGUAUUU
hsa-miR-4694 AGGUGUUAUCCUAUCCAUUUGC CAAAUGGACAGGAUAACACCU
hsa-miR-4695 CAGGAGGCAGUGGGCGAGCAGG UGAUCUCACCGCUGCCUCCUUC
hsa-miR-4696 UGCAAGACGGAUACUGUCAUCU AUGACAGUAUCCGUCUUGCAUU
hsa-miR-4697 AGGGGGCGCAGUCACUGACGUG UGUCAGUGACUCCUGCCCCUUGGU
hsa-miR-4698 UCAAAAUGUAGAGGAAGACCCCA GGGUCUUCCUCUACAUUUUGAUU
hsa-miR-4699 AAUUUACUCUGCAAUCUUCUCC AGAAGAUUGCAGAGUAAGUUCC
hsa-miR-4700 CACAGGACUGACUCCUCACCCCAGUG UCUGGGGAUGAGGACAGUGUGU
hsa-miR-4701 UUGGCCACCACACCUACCCCUU AUGGGUGAUGGGUGUGGUGU
hsa-miR-4703 UGUAGUUGUAUUGUAUUGCCAC UAGCAAUACAGUACAAAUAUAGU
hsa-miR-4704 UCAGUCACAUAUCUAGUGUCUA GACACUAGGCAUGUGAGUGAUU
hsa-miR-4705 UCAAUCACUUGGUAAUUGCUGU AGCAAUUACCAAGUGAUUGAUU
hsa-miR-4706 AGCGGGGAGGAAGUGGGCGCUGCUU GCAGCGCCCACUUCCUCCCCGCUUU
hsa-miR-4707 AGCCCGCCCCAGCCGAGGUUCU GCCCCGGCGCGGGCGGGUUCUGG
hsa-miR-4708 AGAGAUGCCGCCUUGCUCCUU AGCAAGGCGGCAUCUCUCUGAU
hsa-miR-4709 ACAACAGUGACUUGCUCUCCAA UUGAAGAGGAGGUGCUCUGUAGC
hsa-miR-4710 GGGUGAGGGCAGGUGGUU CCACCUGCCCUCACCCUU
hsa-miR-4711 CGUGUCUUCUGGCUUGAU UGCAUCAGGCCAGAAGACAUGAG
hsa-miR-4712 AAUGAGAGACCUGUACUGUAU UCCAGUACAGGUCUCUCAUUUC
hsa-miR-4713 UUCUCCCACUACCAGGCUCCCA UGGGAUCCAGACAGUGGGAGAA
hsa-miR-4714 AACUCUGACCCCUUAGGUUGAU CCAACCUAGGUGGUCAGAGUUG
hsa-miR-4715 GUGCCACCUUAACUGCAGCCAAU AAGUUGGCUGCAGUUAAGGUGG
hsa-miR-4716 AAGGGGGAAGGAAACAUGGAGA UCCAUGUUUCCUUCCCCCUUCU
hsa-miR-4717 ACACAUGGGUGGCUGUGGCCU UAGGCCACAGCCACCCAUGUGU
hsa-miR-4718 AGCUGUACCUGAAACCAAGCA CUUGGUUUCAGGUACAGCUUU
hsa-miR-4719 UCACAAAUCUAUAAUAUGCAGG UGCAUAUUAUAGAUUUGUGAUU
hsa-miR-4720 UGCUUAAGUUGUACCAAGUAU CCUGGCAUAUUUGGUAUAACUU
hsa-miR-4721 UGAGGGCUCCAGGUGACGGUGG ACCGUCACCUGGAGCCCUCAUU
hsa-miR-4722 GGCAGGAGGGCUGUGCCAGGUUG ACCUGCCAGCACCUCCCUGCAG
hsa-miR-4723 UGGGGGAGCCAUGAGAUAAGAGCA CCCUCUCUGGCUCCUCCCCAAA
hsa-miR-4724 AACUGAACCAGGAGUGAGCUUCG GUACCUUCUGGUUCAGCUAGU
hsa-miR-4725 AGACCCUGCAGCCUUCCCACC UGGGGAAGGCGUCAGUGUCGGG
hsa-miR-4726 ACCCAGGUUCCCUCUGGCCGCA AGGGCCAGAGGAGCCUGGAGUGG
hsa-miR-4727 AUAGUGGGAAGCUGGCAGAUUC AUCUGCCAGCUUCCACAGUGG
hsa-miR-4728 CAUGCUGACCUCCCUCCUGCCCCAG UGGGAGGGGAGAGGCAGCAAGCA
hsa-miR-4729 UCAUUUAUCUGUUGGGAAGCUA GCUUCCCAACAGAUAAAUGAUU
hsa-miR-4730 CUGGCGGAGCCCAUUCCAUGCCA GCAUGGAAUGGGCUCCGCCAGUU
hsa-miR-4731 UGCUGGGGGCCACAUGAGUGUG CACACAAGUGGCCCCCAACACU
hsa-miR-4732 UGUAGAGCAGGGAGCAGGAAGCU GCCCUGACCUGUCCUGUUCUG
hsa-miR-4733 AAUCCCAAUGCUAGACCCGGUG CCACCAGGUCUAGCAUUGGGAU
hsa-miR-4734 GCUGCGGGCUGCGGUCAGGGCG CCCUGACCGCAGCCCGCAGCUU
hsa-miR-4735 CCUAAUUUGAACACCUUCGGUA AAAGGUGCUCAAAUUAGACAU
hsa-miR-4736 AGGCAGGUUAUCUGGGCUG GCCCAGAUAACCUGCCUUU
hsa-miR-4737 AUGCGAGGAUGCUGACAGUG CUGUCAGCAUCCUCGCAUUU
hsa-miR-4738 UGAAACUGGAGCGCCUGGAGGA ACCAGCGCGUUUUCAGUUUCAU
hsa-miR-4739 AAGGGAGGAGGAGCGGAGGGGCCCU GGCCCCUCCGCUCCUCCUCCCUUUU
hsa-miR-4740 GCCCGAGAGGAUCCGUCCCUGC AGGACUGAUCCUCUCGGGCAGG
hsa-miR-4741 CGGGCUGUCCGGAGGGGUCGGCU CCGACCCCUCCGGACAGCCCGUU
hsa-miR-4742 UCAGGCAAAGGGAUAUUUACAGA UCUGUAUUCUCCUUUGCCUGCAG
hsa-miR-4743 UUUCUGUCUUUUCUGGUCCAG UGGCCGGAUGGGACAGGAGGCAU
hsa-miR-4744 UCUAAAGACUAGACUUCGCUAUG UAGCGAAGUCUAGUCUUUAGAUU
hsa-miR-4745 UGAGUGGGGCUCCCGGGACGGCG UGGCCCGGCGACGUCUCACGGUC
hsa-miR-4746 AGCGGUGCUCCUGCGGGCCGA CCGGUCCCAGGAGAACCUGCAGA
hsa-miR-4747 AAGGCCCGGGCUUUCCUCCCAG AGGGAAGGAGGCUUGGUCUUAG
hsa-miR-4748 GAGGUUUGGGGAGGAUUUGCU CAAAUCCUCCCCAAACCUCUU
hsa-miR-4749 UGCGGGGACAGGCCAGGGCAUC CGCCCCUCCUGCCCCCACAG
hsa-miR-4750 CCUGACCCACCCCCUCCCGCAG CUCGGGCGGAGGUGGUUGAGUG
hsa-miR-4751 AGAGGACCCGUAGCUGCUAGAAGG UUCUAGCAGCUACGGGUCCUCUUU
hsa-miR-4752 UUGUGGAUCUCAAGGAUGUGCU CACAUCCUUGAGAUCCACAAUU
hsa-miR-4753 CAAGGCCAAAGGAAGAGAACAG UUCUCUUUCUUUAGCCUUGUGU
hsa-miR-4754 AUGCGGACCUGGGUUAGCGGAGU UCCGCUAACCCAGGUCCGCAUUU
hsa-miR-4755 UUUCCCUUCAGAGCCUGGCUUU AGCCAGGCUCUGAAGGGAAAGU
hsa-miR-4756 CCAGAGAUGGUUGCCUUCCUAU CAGGGAGGCGCUCACUCUCUGCU
hsa-miR-4757 CAUGACGUCACAGAGGCUUCGC AGGCCUCUGUGACGUCACGGUGU
hsa-miR-4758 GUGAGUGGGAGCCGGUGGGGCUG UGCCCCACCUGCUGACCACCCUC
hsa-miR-4759 UAGGACUAGAUGUUGGAAUUA AUUCCAACAUCUAGUCCUAUU
hsa-miR-4760 AAAUUCAUGUUCAAUCUAAACC UUUAGAUUGAACAUGAAGUUAG
hsa-miR-4761 ACAAGGUGUGCAUGCCUGACC GAGGGCAUGCGCACUUUGUCC
hsa-miR-4762 CCAAAUCUUGAUCAGAAGCCU CUUCUGAUCAAGAUUUGUGGUG
hsa-miR-4763 AGGCAGGGGCUGGUGCUGGGCGGG CGCCUGCCCAGCCCUCCUGCU
hsa-miR-4764 UUAACUCCUUUCACACCCAUGG UGGAUGUGGAAGGAGUUAUCU
hsa-miR-4765 UGAGUGAUUGAUAGCUAUGUUC ACAUAGCUAUCAAUCACUCAUU
hsa-miR-4766 UCUGAAAGAGCAGUUGGUGUU AUAGCAAUUGCUCUUUUGGAA
hsa-miR-4767 CGCGGGCGCUCCUGGCCGCCGCC CGGCGGCCAGGAGCGCCCGCGUU
hsa-miR-4768 CCAGGAGAUCCAGAGAGAAU AUUCUCUCUGGAUCCCAUGGAU
hsa-miR-4769 UCUGCCAUCCUCCCUCCCCUAC GGUGGGAUGGAGAGAAGGUAUGAG
hsa-miR-4770 UGAGAUGACACUGUAGCU CUACAGUGUCAUCUCAUU
hsa-miR-4771 AGCAGACUUGACCUACAAUUA AUUGUAGGUCAAGUCUGCUUU
hsa-miR-4772 CCUGCAACUUUGCCUGAUCAGA UGAUCAGGCAAAAUUGCAGACU
hsa-miR-4773 CAGAACAGGAGCAUAGAAAGGC CUUUCUAUGCUCCUGUUCUGUU
hsa-miR-4774 AUUGCCUAACAUGUGCCAGAA UCUGGUAUGUAGUAGGUAAUAA
hsa-miR-4775 UUAAUUUUUUGUUUCGGUCACU UGACCGAAACAAAAAAUUAAUU
hsa-miR-4776 GUGGACCAGGAUGGCAAGGGCU CUUGCCAUCCUGGUCCACUGCAU
hsa-miR-4777 UUCUAGAUGAGAGAUAUAUAUA AUACCUCAUCUAGAAUGCUGUA
hsa-miR-4778 UCUUCUUCCUUUGCAGAGUUGA AAUUCUGUAAAGGAAGAAGAGG
hsa-miR-4779 UAGGAGGGAAUAGUAAAAGCAG GCUUUUACUAUUCCCUCCUAUU
hsa-miR-4780 ACCCUUGAGCCUGAUCCCUAGC UAGGGAUCAGGCUCAAGGGUUU
hsa-miR-4781 UAGCGGGGAUUCCAAUAUUGG AAUGUUGGAAUCCUCGCUAGAG
hsa-miR-4782 UGAUUGUCUUCAUAUCUAGAAC UUCUGGAUAUGAAGACAAUCAA
hsa-miR-4783 CCCCGGUGUUGGGGCGCGUCUGC GGCGCGCCCAGCUCCCGGGCU
hsa-miR-4784 UGAGGAGAUGCUGGGACUGA AGUCCCAGCAUCUCCUCAUU
hsa-miR-4785 AGAGUCGGCGACGCCGCCAGC UGGCGGCGUCGCCGACUCUUU
hsa-miR-4786 UGAAGCCAGCUCUGGUCUGGGC UGAGACCAGGACUGGAUGCACC
hsa-miR-4787 GAUGCGCCGCCCACUGCCCCGCGC GCGGGGGUGGCGGCGGCAUCCC
hsa-miR-4788 UUACGGACCAGCUAAGGGAGGC CUCCCUUAGCUGGUCCGUAAUU
hsa-miR-4789 GUAUACACCUGAUAUGUGUAUG CACACAUAGCAGGUGUAUAUA
hsa-miR-4790 AUCGCUUUACCAUUCAUGUU UGAAUGGUAAAGCGAUGUCACA
hsa-miR-4791 UGGAUAUGAUGACUGAAA UCAGUCAUCAUAUCCAUU
hsa-miR-4792 CGGUGAGCGCUCGCUGGC CAGCGAGCGCUCACCGUU
hsa-miR-4793 ACAUCCUGCUCCACAGGGCAGAGG UCUGCACUGUGAGUUGGCUGGCU
hsa-miR-4794 UCUGGCUAUCUCACGAGACUGU AGUCUCGUGAGAUAGCCAGAUU
hsa-miR-4795 AGAAGUGGCUAAUAAUAUUGA AUAUUAUUAGCCACUUCUGGAU
hsa-miR-4796 UAAAGUGGCAGAGUAUAGACAC UGUCUAUACUCUGUCACUUUAC
hsa-miR-4797 GACAGAGUGCCACUUACUGAA UCUCAGUAAGUGGCACUCUGU
hsa-miR-4798 UUCGGUAUACUUUGUGAAUUGG AACUCACGAAGUAUACCGAAGU
hsa-miR-4799 AUCUAAAUGCAGCAUGCCAGUC ACUGGCAUGCUGCAUUUAUAUA
hsa-miR-4800 CAUCCGUCCGUCUGUCCAC AGUGGACCGAGGAAGGAAGGA
hsa-miR-4801 UACACAAGAAAACCAAGGCUCA AGCCUUGGUUUUCUUGUGUAUU
hsa-miR-4802 UAUGGAGGUUCUAGACCAUGUU UACAUGGAUGGAAACCUUCAAGC
hsa-miR-4803 UAACAUAAUAGUGUGGAUUGA AAUCCACACUAUUAUGUUAUU
hsa-miR-4804 UGCUUAACCUUGCCCUCGAAA UUGGACGGUAAGGUUAAGCAA
hsa-miR-483 UCACUCCUCUCCUCCCGUCUU AAGACGGGAGGAAAGAAGGGAG
hsa-miR-484 UCAGGCUCAGUCCCCUCCCGAU CGGGAGGGGACUGAGCCUGAUU
hsa-miR-485 AGAGGCUGGCCGUGAUGAAUUC GUCAUACACGGCUCUCCUCUCU
hsa-miR-486 CGGGGCAGCUCAGUACAGGAU UCCUGUACUGAGCUGCCCCGAG
hsa-miR-487a GUGGUUAUCCCUGCUGUGUUCG AAUCAUACAGGGACAUCCAGUU
hsa-miR-487b GUGGUUAUCCCUGUCCUGUUCG AAUCGUACAGGGUCAUCCACUU
hsa-miR-488 UUGAAAGGCUAUUUCUUGGUC CCCAGAUAAUGGCACUCUCAA
hsa-miR-489 GUGACAUCACAUAUACGGCAGC GGUCGUAUGUGUGACGCCAUUU
hsa-miR-490 CCAUGGAUCUCCAGGUGGGU CAACCUGGAGGACUCCAUGCUG
hsa-miR-491 AGUGGGGAACCCUUCCAUGAGG CUUAUGCAAGAUUCCCUUCUAC
hsa-miR-492 AGGACCUGCGGGACAAGAUUCUU GAAUCUUGUCCCGCAGGUCCUUU
hsa-miR-493 UGAAGGUCUACUGUGUGCCAGG UUGUACAUGGUAGGCUUUCAUU
hsa-miR-494 AGGUUGUCCGUGUUGUCUUCUCU UGAAACAUACACGGGAAACCUC
hsa-miR-495 GAAGUUGCCCAUGUUAUUUUCG AAACAAACAUGGUGCACUUCUU
hsa-miR-496 UGAGUAUUACAUGGCCAAUCUC GAUUGGCCAUGUAAUACUCAUU
hsa-miR-497 CAGCAGCACACUGUGGUUUGU CAAACCACACUGUGGUGUUAGA
hsa-miR-498 UUUCAAGCCAGGGGGCGUUUUUC AAAACGCCCCCUGGCUUGAAAUU
hsa-miR-4999 UGCUGUAUUGUCAGGUAGUGA UCACUACCUGACAAUACAGU
hsa-miR-499a UUAAGACUUGCAGUGAUGUUU AACAUCACAGCAAGUCUGUGCU
hsa-miR-499b ACAGACUUGCUGUGAUGUUCA AACAUCACUGCAAGUCUUAACA
hsa-miR-5000 UCAGGACACUUCUGAACUUGGA CAGUUCAGAAGUGUUCCUGAGU
hsa-miR-5001 AGGGCUGGACUCAGCGGCGGAGCU UUCUGCCUCUGUCCAGGUCCUU
hsa-miR-5002 UGACUGCCUCACUGACCACUU AAUUUGGUUUCUGAGGCACUUAGU
hsa-miR-5003 UCACAACAACCUUGCAGGGUAGA UACUUUUCUAGGUUGUUGGGG
hsa-miR-5004 CUUGGAUUUUCCUGGGCCUCAG UGAGGACAGGGCAAAUUCACGA
hsa-miR-5006 UUGCCAGGGCAGGAGGUGGAA UUUCCCUUUCCAUCCUGGCAG
hsa-miR-5007 UAGAGUCUGGCUGAUAUGGUUU AUCAUAUGAACCAAACUCUAAU
hsa-miR-5008 UGAGGCCCUUGGGGCACAGUGG CCUGUGCUCCCAGGGCCUCGC
hsa-miR-5009 UCCUAAAUCUGAAAGUCCAAAA UUGGACUUUUUCAGAUUUGGGGAU
hsa-miR-500a AUGCACCUGGGCAAGGAUUCUG UAAUCCUUGCUACCUGGGUGAGA
hsa-miR-500b AAUCCUUGCUACCUGGGU GCACCCAGGCAAGGAUUCUG
hsa-miR-501 AAUGCACCCGGGCAAGGAUUCU AAUCCUUUGUCCCUGGGUGAGA
hsa-miR-5010 AGGGGGAUGGCAGAGCAAAAUU UUUUGUGUCUCCCAUUCCCCAG
hsa-miR-5011 UAUAUAUACAGCCAUGCACUC GUGCAUGGCUGUAUAUAUAACA
hsa-miR-502 AAUGCACCUGGGCAAGGAUUCA AUCCUUGCUAUCUGGGUGCUA
hsa-miR-503 UAGCAGCGGGAACAGUUCUGCAG GGGGUAUUGUUUCCGCUGCCAGG
hsa-miR-504 GGGAGUGCAGGGCAGGGUUUC AGACCCUGGUCUGCACUCUAUC
hsa-miR-5047 UUGCAGCUGCGGUUGUAAGGU CUUACAACCGCAGCUGCAAUU
hsa-miR-505 CGUCAACACUUGCUGGUUUCCU GGGAGCCAGGAAGUAUUGAUGU
hsa-miR-506 UAAGGCACCCUUCUGAGUAGA UAUUCAGGAAGGUGUUACUUAA
hsa-miR-507 UUUUGCACCUUUUGGAGUGAA CACUCCAAAAGGUGCAAAAUU
hsa-miR-508 UGAUUGUAGCCUUUUGGAGUAGA UACUCCAGAGGGCGUCACUCAUG
hsa-miR-5087 GGGUUUGUAGCUUUGCUGGCAUG UGCCAGCAAAGCUACAAACCCUU
hsa-miR-5088 UCCCUUCUUCCUGGGCCCUCA CAGGGCUCAGGGAUUGGAUGGAGG
hsa-miR-5089 GUGGGAUUUCUGAGUAGCAUC AUGCUACUCGGAAAUCCCACUGA
hsa-miR-509-1 UGAUUGGUACGUCUGUGGGUAG UACUGCAGACAGUGGCAAUCA
hsa-miR-509-3 UGAUUGGUACGUCUGUGGGUAG UACUGCAGACGUGGCAAUCAUG
hsa-miR-5090 CCGGGGCAGAUUGGUGUAGGGUG CCCUACACCAAUCUGCCCCGGUU
hsa-miR-5091 ACGGAGACGACAAGACUGUGCUG GCACAGUCUUGUCGUCUCCGUUU
hsa-miR-5092 AAUCCACGCUGAGCUUGGCAUC UGCCAAGCUCAGCGUGGAUUUU
hsa-miR-5093 AGGAAAUGAGGCUGGCUAGGAGC UCCUAGCCAGCCUCAUUUCCUUU
hsa-miR-5094 AAUCAGUGAAUGCCUUGAACCU GUUCAAGGCAUUCACUGAUUUU
hsa-miR-5095 UUACAGGCGUGAACCACCGCG CGGUGGUUCACGCCUGUAAUU
hsa-miR-5096 GUUUCACCAUGUUGGUCAGGC CUGACCAACAUGGUGAAACUU
hsa-miR-510 UACUCAGGAGAGUGGCAAUCAC AUUGAAACCUCUAAGAGUGGA
hsa-miR-5100 UUCAGAUCCCAGCGGUGCCUCU AGGCACCGCUGGGAUCUGAAUU
hsa-miR-511 GUGUCUUUUGCUCUGCAGUCA AAUGUGUAGCAAAAGACAGA
hsa-miR-512 AAGUGCUGUCAUAGCUGAGGUC CACUCAGCCUUGAGGGCACUUUC
hsa-miR-513a UAAAUUUCACCUUUCUGAGAAGG UUCACAGGGAGGUGUCAU
hsa-miR-513b AAAUGUCACCUUUUUGAGAGGA UUCACAAGGAGGUGUCAUUUAU
hsa-miR-513c UUCUCAAGGAGGUGUCGUUUAU UAAAUUUCACCUUUCUGAGAAGA
hsa-miR-514a AUUGACACUUCUGUGAGUAGA UACUCUGGAGAGUGACAAUCAUG
hsa-miR-514b AUUGACACCUCUGUGAGUGGA UUCUCAAGAGGGAGGCAAUCAU
hsa-miR-515 GAGUGCCUUCUUUUGGAGCGUU UUCUCCAAAAGAAAGCACUUUCUG
hsa-miR-516a UUCUCGAGGAAAGAAGCACUUUC UGCUUCCUUUCAGAGGGU
hsa-miR-516b AUCUGGAGGUAAGAAGCACUUU UGCUUCCUUUCAGAGGGU
hsa-miR-517a AUCGUGCAUCCCUUUAGAGUGU CCUCUAGAUGGAAGCACUGUCU
hsa-miR-517b AUCGUGCAUCCCUUUAGAGUGU CCUCUAGAUGGAAGCACUGUCU
hsa-miR-517c AUCGUGCAUCCUUUUAGAGUGU CCUCUAGAUGGAAGCACUGUCU
hsa-miR-5186 AGAGAUUGGUAGAAAUCAGGU CUGAUUUCUACCAAUCUCUUU
hsa-miR-5187 ACUGAAUCCUCUUUUCCUCAG UGGGAUGAGGGAUUGAAGUGGA
hsa-miR-5188 AAUCGGACCCAUUUAAACCGGAG CCGGUUUAAAUGGGUCCGAUUUU
hsa-miR-5189 UCUGGGCACAGGCGGAUGGACAGG UGCCAACCGUCAGAGCCCAGA
hsa-miR-518a GAAAGCGCUUCCCUUUGCUGGA CUGCAAAGGGAAGCCCUUUC
hsa-miR-518b CAAAGCGCUCCCCUUUAGAGGU CUCUAAAGGGGAGCGCUUUGUU
hsa-miR-518c CAAAGCGCUUCUCUUUAGAGUGU UCUCUGGAGGGAAGCACUUUCUG
hsa-miR-518d CUCUAGAGGGAAGCACUUUCUG CAAAGCGCUUCCCUUUGGAGC
hsa-miR-518e CUCUAGAGGGAAGCGCUUUCUG AAAGCGCUUCCCUUCAGAGUG
hsa-miR-518f CUCUAGAGGGAAGCACUUUCUC GAAAGCGCUUCUCUUUAGAGG
hsa-miR-5190 CCAGUGACUGAGCUGGAGCCA GCUCCAGCUCAGUCACUGGUU
hsa-miR-5191 AGGAUAGGAAGAAUGAAGUGCU CACUUCAUUCUUCCUAUCCUUU
hsa-miR-5192 AGGAGAGUGGAUUCCAGGUGGU CACCUGGAAUCCACUCUCCUUU
hsa-miR-5193 UCCUCCUCUACCUCAUCCCAGU UGGGAUGAGGUAGAGGAGGAUU
hsa-miR-5194 UGAGGGGUUUGGAAUGGGAUGG AUCCCAUUCCAAACCCCUCAUU
hsa-miR-5195 AACCCCUAAGGCAACUGGAUGG AUCCAGUUCUCUGAGGGGGCU
hsa-miR-5196 AGGGAAGGGGACGAGGGUUGGG UCAUCCUCGUCUCCCUCCCAG
hsa-miR-5197 AAGAAGAGACUGAGUCAUCGAAU CAAUGGCACAAACUCAUUCUUGA
hsa-miR-519a CUCUAGAGGGAAGCGCUUUCUG AAAGUGCAUCCUUUUAGAGUGU
hsa-miR-519b AAAGUGCAUCCUUUUAGAGGUU CUCUAGAGGGAAGCGCUUUCUG
hsa-miR-519c AAAGUGCAUCUUUUUAGAGGAU CUCUAGAGGGAAGCGCUUUCUG
hsa-miR-519d CAAAGUGCCUCCCUUUAGAGUG CCUCCAAAGGGAAGCGCUUUCUGUU
hsa-miR-519e UUCUCCAAAAGGGAGCACUUUC AAGUGCCUCCUUUUAGAGUGUU
hsa-miR-520a AAAGUGCUUCCCUUUGGACUGU CUCCAGAGGGAAGUACUUUCU
hsa-miR-520b AAAGUGCUUCCUUUUAGAGGG CUCUAAAAGGAAGCACUUUUU
hsa-miR-520c CUCUAGAGGGAAGCACUUUCUG AAAGUGCUUCCUUUUAGAGGGU
hsa-miR-520d CUACAAAGGGAAGCCCUUUC AAAGUGCUUCUCUUUGGUGGGU
hsa-miR-520e AAAGUGCUUCCUUUUUGAGGG CUCAAAAAGGAAGCACUUUUU
hsa-miR-520f CCUCUAAAGGGAAGCGCUUUCU AAGUGCUUCCUUUUAGAGGGUU
hsa-miR-520g UCUAGAGGAAGCACUUUCUGUUU ACAAAGUGCUUCCCUUUAGAGUGU
hsa-miR-520h ACAAAGUGCUUCCCUUUAGAGU UCUAAAGGGAAGCACUUUGUUU
hsa-miR-521 AACGCACUUCCCUUUAGAGUGU ACUCUAAAGGGAAGUGCGUUUU
hsa-miR-522 CUCUAGAGGGAAGCGCUUUCUG AAAAUGGUUCCCUUUAGAGUGU
hsa-miR-523 CUCUAGAGGGAAGCGCUUUCUG GAACGCGCUUCCCUAUAGAGGGU
hsa-miR-524 GAAGGCGCUUCCCUUUGGAGU CUACAAAGGGAAGCACUUUCUC
hsa-miR-525 CUCCAGAGGGAUGCACUUUCU GAAGGCGCUUCCCUUUAGAGCG
hsa-miR-526a CUCUAGAGGGAAGCACUUUCUG GAAAGUGCUUCCCUCUAGAGUU
hsa-miR-526b GAAAGUGCUUCCUUUUAGAGGC CUCUUGAGGGAAGCACUUUCUGU
hsa-miR-527 CUGCAAAGGGAAGCCCUUUC AAGGGCUUCCCUUUGCAGUU
hsa-miR-532 CCUCCCACACCCAAGGCUUGCA CAUGCCUUGAGUGUAGGACCGU
hsa-miR-539 GGAGAAAUUAUCCUUGGUGUGU AUCAUACAAGGACAAUUUCUUU
hsa-miR-541 UGGUGGGCACAGAAUCUGGACU AAAGGAUUCUGCUGUCGGUCCCACU
hsa-miR-542 UGUGACAGAUUGAUAACUGAAA UCGGGGAUCAUCAUGUCACGAGA
hsa-miR-543 AAACAUUCGCGGUGCACUUCUU GAAGUGCACCGCGAAUGUUUUU
hsa-miR-544a AUUCUGCAUUUUUAGCAAGUUC ACUUGCUAAAAAUGCAGAAUUU
hsa-miR-544b ACCUGAGGUUGUGCAUUUCUAA AGAAAUGCACAACCUCAGGUUU
hsa-miR-545 UCAGUAAAUGUUUAUUAGAUGA UCAGCAAACAUUUAUUGUGUGC
hsa-miR-548a CAAAACUGGCAAUUACUUUUGC AAAAGUAAUUGCGAGUUUUACC
hsa-miR-548aa AAAAACCACAAUUACUUUUGCACCA GUGCAAAAGUAAUUGUGGUUUUUUU
hsa-miR-548ab AAAAGUAAUUGUGGAUUUUGCU CAAAAUCCACAAUUACUUUUUU
hsa-miR-548ac CAAAAACCGGCAAUUACUUUUG AAAGUAAUUGCCGGUUUUUGUU
hsa-miR-548ad AAAAGUAAUUGUGGUUUUUG GAAAACGACAAUGACUUUUGCA
hsa-miR-548ae CAAAAACUGCAAUUACUUUCA AAAAGUAAUUGUGGUUUUUG
hsa-miR-548ag AAAGGUAAUUGUGGUUUCUGC AGAAACCACAAUUACCUUUUU
hsa-miR-548ah CAAAAACUGCAGUUACUUUUGC AAAAGUGAUUGCAGUGUUUG
hsa-miR-548ai AAAGGUAAUUGCAGUUUUUCCC GAAAAACUGCAAUUACCUUUUU
hsa-miR-548aj UGCAAAAGUAAUUGCAGUUUUUG UAAAAACUGCAAUUACUUUUA
hsa-miR-548ak AAAAGUAACUGCGGUUUUUGA AAAAACCGCAGUUACUUUUUU
hsa-miR-548al AACGGCAAUGACUUUUGUACCA GUACAAAAGUCAUUGCCGUUUU
hsa-miR-548am AAAAGUAAUUGCGGUUUUUGCC CAAAAACUGCAGUUACUUUUGU
hsa-miR-548an AAAAGGCAUUGUGGUUUUUG AAAACCACAAUGCCUUUUUU
hsa-miR-548ao AGAAGUAACUACGGUUUUUGCA AAAGACCGUGACUACUUUUGCA
hsa-miR-548ap AAAAGUAAUUGCGGUCUUU AAAAACCACAAUUACUUUU
hsa-miR-548aq GAAAGUAAUUGCUGUUUUUGCC CAAAAACUGCAAUUACUUUUGC
hsa-miR-548ar AAAAGUAAUUGCAGUUUUUGC UAAAACUGCAGUUAUUUUUGC
hsa-miR-548as UAAAACCCACAAUUAUGUUUGU AAAAGUAAUUGCGGGUUUUGCC
hsa-miR-548at AAAAGUUAUUGCGGUUUUGGCU CAAAACCGCAGUAACUUUUGU
hsa-miR-548au UGGCAGUUACUUUUGCACCAG AAAAGUAAUUGCGGUUUUUGC
hsa-miR-548av AAAACUGCAGUUACUUUUGC AAAAGUACUUGCGGAUUU
hsa-miR-548aw GUGCAAAAGUCAUCACGGUU CCGUGAUGACUUUUGCACUU
hsa-miR-548ax AGAAGUAAUUGCGGUUUUGCCA GCAAAACCGCAAUUACUUCUUU
hsa-miR-548ay CAAAACCGCGAUUACUCUUGCA AAAAGUAAUUGUGGUUUUUGC
hsa-miR-548az AAAAACUGCAAUCACUUUUGC CAAAAGUGAUUGUGGUUUUUGC
hsa-miR-548b AAAAGUAAUUGUGGUUUUGGCC CAAGAACCUCAGUUGCUUUUGU
hsa-miR-548ba AAAGGUAACUGUGAUUUUUGCU CAAAAAUCACAGUUACCUUUUU
hsa-miR-548bb AAAAGUAACUAUGGUUUUUGCC CAAAAACCAUAGUUACUUUUGC
hsa-miR-548c AAAAGUAAUUGCGGUUUUUGCC CAAAAAUCUCAAUUACUUUUGC
hsa-miR-548d CAAAAACCACAGUUUCUUUUGC AAAAGUAAUUGUGGUUUUUGCC
hsa-miR-548e AAAAACUGAGACUACUUUUGCA CAAAAGCAAUCGCGGUUUUUGC
hsa-miR-548f AAAAACUGUAAUUACUUUU UGCAAAAGUAAUCACAGUUUUU
hsa-miR-548g UGCAAAAGUAAUUGCAGUUUUUG AAAACUGUAAUUACUUUUGUAC
hsa-miR-548h CAAAAACCGCAAUUACUUUUGCA AAAAGUAAUCGCGGUUUUUGUC
hsa-miR-548i AAAAGUAAUUGCGGAUUUUGCC CAAAAUCCGCAAUUACUUUUUU
hsa-miR-548j CAAAAACUGCAUUACUUUUGC AAAAGUAAUUGCGGUCUUUGGU
hsa-miR-548k AAAAGUACUUGCGGAUUUUGCU CAAAAUCCGCAAGUACUUUUUU
hsa-miR-548l AAAAGUAUUUGCGGGUUUUGUC CAAAACCCGCAAAUACUUUUUU
hsa-miR-548m CAAAGGUAUUUGUGGUUUUUG AAAACCACAAAUACCUUUGUU
hsa-miR-548n CAAAAGUAAUUGUGGAUUUUGU AAAAUCCACAAUUACUUUUGUU
hsa-miR-548o CCAAAACUGCAGUUACUUUUGC AAAAGUAAUUGCGGUUUUUGCC
hsa-miR-548p UAGCAAAAACUGCAGUUACUUU AGUAACUGCAGUUUUUGCUAUU
hsa-miR-548q GCUGGUGCAAAAGUAAUGGCGG GCCAUUACUUUUGCACCAGCUU
hsa-miR-548s AUGGCCAAAACUGCAGUUAUUUU AAUAACUGCAGUUUUGGCCAUUU
hsa-miR-548t AAAAACCACAAUUACUUUUGCACCA CAAAAGUGAUCGUGGUUUUUG
hsa-miR-548u CAAAGACUGCAAUUACUUUUGCG CAAAAGUAAUUGCAGUCUUUGUU
hsa-miR-548v AGCUACAGUUACUUUUGCACCA GUGCAAAAGUAACUGUAGCUUU
hsa-miR-548w AAAAGUAACUGCGGUUUUUGCCU GCAAAAACCGCAGUUACUUUUUU
hsa-miR-548x UGCAAAAGUAAUUGCAGUUUUUG UAAAAACUGCAAUUACUUUC
hsa-miR-548y AAAAGUAAUCACUGUUUUUGCC CAAAAACAGUGAUUACUUUUUU
hsa-miR-548z CAAAAACCGCAAUUACUUUUGCA CAAAAGUAAUUGCGGUUUUUGUU
hsa-miR-549a UGACAACUAUGGAUGAGCUCU AGCUCAUCCAUAGUUGUCAUU
hsa-miR-550a-1 UGUCUUACUCCCUCAGGCACAU AGUGCCUGAGGGAGUAAGAGCCC
hsa-miR-550a-3 UGUCUUACUCCCUCAGGCACAU AGUGCCUGAGGGAGUAAGAG
hsa-miR-550b UCUUACUCCCUCAGGCACUG AUGUGCCUGAGGGAGUAAGACA
hsa-miR-551a GCGACCCACUCUUGGUUUCCA GAAACCAAGAGUGGGUCGCUU
hsa-miR-551b GAAAUCAAGCGUGGGUGAGACC GCGACCCAUACUUGGUUUCAG
hsa-miR-552 GUUUAACCUUUUGCCUGUUGG AACAGGUGACUGGUUAGACAA
hsa-miR-553 AAAACGGUGAGAUUUUGUUUU AACAAAAUCUCACCGUUUUUU
hsa-miR-554 GCUAGUCCUGACUCAGCCAGU UGGCUGAGUCAGGACUAGCUU
hsa-miR-555 AGGGUAAGCUGAACCUCUGAU CAGAGGUUCAGCUUACCCUUU
hsa-miR-556 GAUGAGCUCAUUGUAAUAUGAG AUAUUACCAUUAGCUCAUCUUU
hsa-miR-557 GUUUGCACGGGUGGGCCUUGUCU ACAAGGCCCACCCGUGCAAACUU
hsa-miR-5571 GUCCUAGGAGGCUCCUCUG CAAUUCUCAAAGGAGCCUCCC
hsa-miR-5572 GUUGGGGUGCAGGGGUCUGCU CAGACCCCUGCACCCCAACUU
hsa-miR-5579 UAUGGUACUCCUUAAGCUAAC UUAGCUUAAGGAGUACCAGAUC
hsa-miR-558 UGAGCUGCUGUACCAAAAU UUUGGUACAGCAGCUCAUU
hsa-miR-5580 CACAUAUGAAGUGAGCCAGCAC UGCUGGCUCAUUUCAUAUGUGU
hsa-miR-5581 AGCCUUCCAGGAGAAAUGGAGA UUCCAUGCCUCCUAGAAGUUCC
hsa-miR-5582 UAAAACUUUAAGUGUGCCUAGG UAGGCACACUUAAAGUUAUAGC
hsa-miR-5583 GAAUAUGGGUAUAUUAGUUUGG AAACUAAUAUACCCAUAUUCUG
hsa-miR-5584 CAGGGAAAUGGGAAGAACUAGA UAGUUCUUCCCUUUGCCCAAUU
hsa-miR-5585 CUGAAUAGCUGGGACUACAGGU UGAAGUACCAGCUACUCGAGAG
hsa-miR-5586 UAUCCAGCUUGUUACUAUAUGC CAGAGUGACAAGCUGGUUAAAG
hsa-miR-5587 AUGGUCACCUCCGGGACU GCCCCGGGCAGUGUGAUCAUC
hsa-miR-5588 ACUGGCAUUAGUGGGACUUUU AAGUCCCACUAAUGCCAGC
hsa-miR-5589 GGCUGGGUGCUCUUGUGCAGU UGCACAUGGCAACCUAGCUCCCA
hsa-miR-559 UAAAGUAAAUAUGCACCAAAA UUGGUGCAUAUUUACUUUAUU
hsa-miR-5590 AAUAAAGUUCAUGUAUGGCAA UUGCCAUACAUAGACUUUAUU
hsa-miR-5591 UGGGAGCUAAGCUAUGGGUAU AUACCCAUAGCUUAGCUCCCA
hsa-miR-561 CAAAGUUUAAGAUCCUUGAAGU AUCAAGGAUCUUAAACUUUGCC
hsa-miR-562 AAAGUAGCUGUACCAUUUGC AAAUGGUACAGCUACUUUUU
hsa-miR-563 AGGUUGACAUACGUUUCCC GAAACGUAUGUCAACCUUU
hsa-miR-564 AGGCACGGUGUCAGCAGGC CUGCUGACACCGUGCCUUU
hsa-miR-566 GGGCGCCUGUGAUCCCAAC UGGGAUCACAGGCGCCCUU
hsa-miR-567 AGUAUGUUCUUCCAGGACAGAAC UCUGUCCUGGAAGAACAUACUUU
hsa-miR-568 AUGUAUAAAUGUAUACACAC GUGUAUACAUUUAUACAUUU
hsa-miR-5680 GAGAAAUGCUGGACUAAUCUGC AGAUUAGUCCAGCAUUUCUCUU
hsa-miR-5681a AGAAAGGGUGGCAAUACCUCUU GAGGUAUUGCCACCCUUUCUUU
hsa-miR-5681b AGGUAUUGCCACCCUUUCUAGU UAGAAAGGGUGGCAAUACCUUU
hsa-miR-5682 GUAGCACCUUGCAGGAUAAGGU CUUAUCCUGCAAGGUGCUACUU
hsa-miR-5683 UACAGAUGCAGAUUCUCUGACUUC AGUCAGAGAAUCUGCAUCUGUAUU
hsa-miR-5684 AACUCUAGCCUGAGCAACAG GUUGCUCAGGCUAGAGUUUU
hsa-miR-5685 ACAGCCCAGCAGUUAUCACGGG CGUGAUAACUGCUGGGCUGUUU
hsa-miR-5687 UUAGAACGUUUUAGGGUCAAAU UUGACCCUAAAACGUUCUAAUU
hsa-miR-5688 UAACAAACACCUGUAAAACAGC UGUUUUACAGGUGUUUGUUAUU
hsa-miR-5689 AGCAUACACCUGUAGUCCUAGA UAGGACUACAGGUGUAUGCUUU
hsa-miR-569 AGUUAAUGAAUCCUGGAAAGU UUUCCAGGAUUCAUUAACUUU
hsa-miR-5690 UCAGCUACUACCUCUAUUAGG UAAUAGAGGUAGUAGCUGAUU
hsa-miR-5691 UUGCUCUGAGCUCCGAGAAAGC UUUCUCGGAGCUCAGAGCAAUU
hsa-miR-5692a CAAAUAAUACCACAGUGGGUGU ACCCACUGUGGUAUUAUUUGUU
hsa-miR-5692b AAUAAUAUCACAGUAGGUGU ACCUACUGUGAUAUUAUUUU
hsa-miR-5692c AAUAAUAUCACAGUAGGUGUAC ACACCUACUGUGAUAUUAUUUU
hsa-miR-5693 GCAGUGGCUCUGAAAUGAACUC GUUCAUUUCAGAGCCACUGCUU
hsa-miR-5694 CAGAUCAUGGGACUGUCUCAG GAGACAGUCCCAUGAUCUGUU
hsa-miR-5695 ACUCCAAGAAGAAUCUAGACAG GUCUAGAUUCUUCUUGGAGUUU
hsa-miR-5696 CUCAUUUAAGUAGUCUGAUGCC CAUCAGACUACUUAAAUGAGUU
hsa-miR-5697 UCAAGUAGUUUCAUGAUAAAGG UUUAUCAUGAAACUACUUGAUU
hsa-miR-5698 UGGGGGAGUGCAGUGAUUGUGG ACAAUCACUGCACUCCCCCAUU
hsa-miR-5699 UCCUGUCUUUCCUUGUUGGAGC UGCCCCAACAAGGAAGGACAAG
hsa-miR-570 CGAAAACAGCAAUUACCUUUGC AAAGGUAAUUGCAGUUUUUCCC
hsa-miR-5700 UAAUGCAUUAAAUUAUUGAAGG UUCAAUAAUUUAAUGCAUUAUU
hsa-miR-5701 UUAUUGUCACGUUCUGAUU UCAGAACGUGACAAUAAUU
hsa-miR-5702 UGAGUCAGCAACAUAUCCCAUG UGGGAUAUGUUGCUGACUCAUU
hsa-miR-5703 AGGAGAAGUCGGGAAGGU CUUCCCGACUUCUCCUUU
hsa-miR-5704 UUAGGCCAUCAUCCCAUUAUGC AUAAUGGGAUGAUGGCCUAAUU
hsa-miR-5705 UGUUUCGGGGCUCAUGGCCUGUG CAGGCCAUGAGCCCCGAAACAUU
hsa-miR-5706 UUCUGGAUAACAUGCUGAAGCU CUUCAGCAUGUUAUCCAGAAUU
hsa-miR-5707 ACGUUUGAAUGCUGUACAAGGC CUUGUACAGCAUUCAAACGUUU
hsa-miR-5708 AUGAGCGACUGUGCCUGACC UCAGGCACAGUCGCUCAUUU
hsa-miR-571 UGAGUUGGCCAUCUGAGUGAG CACUCAGAUGGCCAACUCAUU
hsa-miR-572 GUCCGCUCGGCGGUGGCCCA GGCCACCGCCGAGCGGACUU
hsa-miR-573 CUGAAGUGAUGUGUAACUGAUCAG GAUCAGUUACACAUCACUUCAGUU
hsa-miR-5739 GCGGAGAGAGAAUGGGGAGC UCCCCAUUCUCUCUCCGCUU
hsa-miR-574 UGAGUGUGUGUGUGUGAGUGUGU CACGCUCAUGCACACACCCACA
hsa-miR-575 GAGCCAGUUGGACAGGAGC UCCUGUCCAACUGGCUCUU
hsa-miR-576 AAGAUGUGGAAAAAUUGGAAUC AUUCUAAUUUCUCCACGUCUUU
hsa-miR-577 UAGAUAAAAUAUUGGUACCUG GGUACCAAUAUUUUAUCUAUU
hsa-miR-578 CUUCUUGUGCUCUAGGAUUGU AAUCCUAGAGCACAAGAAGUU
hsa-miR-5787 GGGCUGGGGCGCGGGGAGGU CUCCCCGCGCCCCAGCCCUU
hsa-miR-579 UUCAUUUGGUAUAAACCGCGAUU UCGCGGUUUGUGCCAGAUGACG
hsa-miR-580 UAAUGAUUCAUCAGACUCAGAU UUGAGAAUGAUGAAUCAUUAGG
hsa-miR-581 UCUUGUGUUCUCUAGAUCAGU UGAUCUAGAGAACACAAGAUU
hsa-miR-582 UUACAGUUGUUCAACCAGUUACU UAACUGGUUGAACAACUGAACC
hsa-miR-583 CAAAGAGGAAGGUCCCAUUAC AAUGGGACCUUCCUCUUUGUU
hsa-miR-584 UUAUGGUUUGCCUGGGACUGAG UCAGUUCCAGGCCAACCAGGCU
hsa-miR-585 UGGGCGUAUCUGUAUGCUA CUAGCACACAGAUACGCCCAGA
hsa-miR-586 UAUGCAUUGUAUUUUUAGGUCC ACCUAAAAAUACAAUGCAUAUU
hsa-miR-587 UUUCCAUAGGUGAUGAGUCAC GACUCAUCACCUAUGGAAAUU
hsa-miR-588 UUGGCCACAAUGGGUUAGAAC UCUAACCCAUUGUGGCCAAUU
hsa-miR-589 UCAGAACAAAUGCCGGUUCCCAGA UGAGAACCACGUCUGCUCUGAG
hsa-miR-590 GAGCUUAUUCAUAAAAGUGCAG UAAUUUUAUGUAUAAGCUAGU
hsa-miR-591 AGACCAUGGGUUCUCAUUGU AAUGAGAACCCAUGGUCUUU
hsa-miR-592 UUGUGUCAAUAUGCGAUGAUGU AUCAUCGCAUAUUGACACAAUU
hsa-miR-593 UGUCUCUGCUGGGGUUUCU AGGCACCAGCCAGGCAUUGCUCAGC
hsa-miR-595 GAAGUGUGCCGUGGUGUGUCU ACACACCACGGCACACUUCUU
hsa-miR-596 AAGCCUGCCCGGCUCCUCGGG CGAGGAGCCGGGCAGGCUUUU
hsa-miR-597 UGGUUCUCUUGUGGCUCAAGCGU UGUGUCACUCGAUGACCACUGU
hsa-miR-598 UACGUCAUCGUUGUCAUCGUCA GCGGUGAUCCCGAUGGUGUGAGC
hsa-miR-599 GUUGUGUCAGUUUAUCAAAC UUGAUAAACUGACACAACUU
hsa-miR-600 ACUUACAGACAAGAGCCUUGCUC GCAAGGCUCUUGUCUGUAAGUUU
hsa-miR-601 UGGUCUAGGAUUGUUGGAGGAG CCUCCAACAAUCCUAGACCAUU
hsa-miR-602 GACACGGGCGACAGCUGCGGCCC GCCGCAGCUGUCGCCCGUGUCUU
hsa-miR-603 CACACACUGCAAUUACUUUUGC AAAAGUAAUUGCAGUGUGUGUU
hsa-miR-604 AGGCUGCGGAAUUCAGGAC CCUGAAUUCCGCAGCCUUU
hsa-miR-605 AGAAGGCACUAUGAGAUUUAGA UAAAUCCCAUGGUGCCUUCUCCU
hsa-miR-606 AAACUACUGAAAAUCAAAGAU CUUUGAUUUUCAGUAGUUUUU
hsa-miR-6068 CCUGCGAGUCUCCGGCGGUGG ACCGCCGGAGACUCGCAGGUU
hsa-miR-6069 GGGCUAGGGCCUGCUGCCCCC GGGCAGCAGGCCCUAGCCCUU
hsa-miR-607 GUUCAAAUCCAGAUCUAUAAC UAUAGAUCUGGAUUUGAACUU
hsa-miR-6070 CCGGUUCCAGUCCCUGGAG CCAGGGACUGGAACCGGUU
hsa-miR-6071 UUCUGCUGCCGGCCAAGGC CUUGGCCGGCAGCAGAAUU
hsa-miR-6072 UCCUCAUCACACUGCACCUUAG AAGGUGCAGUGUGAUGAGGAUU
hsa-miR-6073 GGUAGUGAGUUAUCAGCUAC AGCUGAUAACUCACUACCUU
hsa-miR-6074 GAUAUUCAGAGGCUAGGUGG ACCUAGCCUCUGAAUAUCUU
hsa-miR-6075 ACGGCCCAGGCGGCAUUGGUG CCAAUGCCGCCUGGGCCGUUU
hsa-miR-6076 AGCAUGACAGAGGAGAGGUGG ACCUCUCCUCUGUCAUGCUUU
hsa-miR-6077 GGGAAGAGCUGUACGGCCUUC AGGCCGUACAGCUCUUCCCUU
hsa-miR-6078 CCGCCUGAGCUAGCUGUGG ACAGCUAGCUCAGGCGGUU
hsa-miR-6079 UUGGAAGCUUGGACCAACUAGCUG GCUAGUUGGUCCAAGCUUCCAAUU
hsa-miR-608 AGGGGUGGUGUUGGGACAGCUCCGU GGAGCUGUCCCAACACCACCCCUUU
hsa-miR-6080 UCUAGUGCGGGCGUUCCCG GGAACGCCCGCACUAGAUU
hsa-miR-6081 AGGAGCAGUGCCGGCCAAGGCGCC CGCCUUGGCCGGCACUGCUCCUUU
hsa-miR-6082 GAAUACGUCUGGUUGAUCC AUCAACCAGACGUAUUCUU
hsa-miR-6083 CUUAUAUCAGAGGCUGUGGG CACAGCCUCUGAUAUAAGUU
hsa-miR-6084 UUCCGCCAGUCGGUGGCCGG GGCCACCGACUGGCGGAAUU
hsa-miR-6085 AAGGGGCUGGGGGAGCACA UGCUCCCCCAGCCCCUUUU
hsa-miR-6086 GGAGGUUGGGAAGGGCAGAG CUGCCCUUCCCAACCUCCUU
hsa-miR-6087 UGAGGCGGGGGGGCGAGC UCGCCCCCCCGCCUCAUU
hsa-miR-6088 AGAGAUGAAGCGGGGGGGCG CCCCCCCGCUUCAUCUCUUU
hsa-miR-6089 GGAGGCCGGGGUGGGGCGGGGCGG GCCCCGCCCCACCCCGGCCUCCUU
hsa-miR-609 AGGGUGUUUCUCUCAUCUCU AGAUGAGAGAAACACCCUUU
hsa-miR-6090 GGGGAGCGAGGGGCGGGGC CCCGCCCCUCGCUCCCCUU
hsa-miR-610 UGAGCUAAAUGUGUGCUGGGA CCAGCACACAUUUAGCUCAUU
hsa-miR-611 GCGAGGACCCCUCGGGGUCUGAC CAGACCCCGAGGGGUCCUCGCUU
hsa-miR-612 GCUGGGCAGGGCUUCUGAGCUCCUU GGAGCUCAGAAGCCCUGCCCAGCUU
hsa-miR-6124 GGGAAAAGGAAGGGGGAGGA CUCCCCCUUCCUUUUCCCUU
hsa-miR-6125 GCGGAAGGCGGAGCGGCGGA CGCCGCUCCGCCUUCCGCUU
hsa-miR-6126 GUGAAGGCCCGGCGGAGA UCCGCCGGGCCUUCACUU
hsa-miR-6127 UGAGGGAGUGGGUGGGAGG UCCCACCCACUCCCUCAUU
hsa-miR-6128 ACUGGAAUUGGAGUCAAAA UUGACUCCAAUUCCAGUUU
hsa-miR-6129 UGAGGGAGUUGGGUGUAUA UACACCCAACUCCCUCAUU
hsa-miR-613 AGGAAUGUUCCUUCUUUGCC CAAAGAAGGAACAUUCCUUU
hsa-miR-6130 UGAGGGAGUGGAUUGUAUG UACAAUCCACUCCCUCAUU
hsa-miR-6131 GGCUGGUCAGAUGGGAGUG CUCCCAUCUGACCAGCCUU
hsa-miR-6132 AGCAGGGCUGGGGAUUGCA CAAUCCCCAGCCCUGCUUU
hsa-miR-6133 UGAGGGAGGAGGUUGGGUA CCCAACCUCCUCCCUCAUU
hsa-miR-6134 UGAGGUGGUAGGAUGUAGA UACAUCCUACCACCUCAUU
hsa-miR-614 GAACGCCUGUUCUUGCCAGGUGG ACCUGGCAAGAACAGGCGUUCUU
hsa-miR-615 GGGGGUCCCCGGUGCUCGGAUC UCCGAGCCUGGGUCUCCCUCUU
hsa-miR-616 ACUCAAAACCCUUCAGUGACUU AGUCAUUGGAGGGUUUGAGCAG
hsa-miR-6165 CAGCAGGAGGUGAGGGGAG CCCCUCACCUCCUGCUGUU
hsa-miR-617 AGACUUCCCAUUUGAAGGUGGC CACCUUCAAAUGGGAAGUCUUU
hsa-miR-618 AAACUCUACUUGUCCUUCUGAGU UCAGAAGGACAAGUAGAGUUUUU
hsa-miR-619 GCUGGGAUUACAGGCAUGAGCC GACCUGGACAUGUUUGUGCCCAGU
hsa-miR-620 AUGGAGAUAGAUAUAGAAAU UUCUAUAUCUAUCUCCAUUU
hsa-miR-621 GGCUAGCAACAGCGCUUACCU GUAAGCGCUGUUGCUAGCCUU
hsa-miR-622 ACAGUCUGCUGAGGUUGGAGC UCCAACCUCAGCAGACUGUUU
hsa-miR-623 AUCCCUUGCAGGGGCUGUUGGGU CCAACAGCCCCUGCAAGGGAUUU
hsa-miR-624 UAGUACCAGUACCUUGUGUUCA CACAAGGUAUUGGUAUUACCU
hsa-miR-625 AGGGGGAAAGUUCUAUAGUCC GACUAUAGAACUUUCCCCCUCA
hsa-miR-626 AGCUGUCUGAAAAUGUCUU GACAUUUUCAGACAGCUUU
hsa-miR-627 UCUUUUCUUUGAGACUCACU GUGAGUCUCUAAGAAAAGAGGA
hsa-miR-628 UCUAGUAAGAGUGGCAGUCGA AUGCUGACAUAUUUACUAGAGG
hsa-miR-629 UGGGUUUACGUUGGGAGAACU GUUCUCCCAACGUAAGCCCAGC
hsa-miR-630 AGUAUUCUGUACCAGGGAAGGU CUUCCCUGGUACAGAAUACUUU
hsa-miR-631 AGACCUGGCCCAGACCUCAGC UGAGGUCUGGGCCAGGUCUUU
hsa-miR-632 GUGUCUGCUUCCUGUGGGA CCACAGGAAGCAGACACUU
hsa-miR-633 CUAAUAGUAUCUACCACAAUAAA UAUUGUGGUAGAUACUAUUAGUU
hsa-miR-634 AACCAGCACCCCAACUUUGGAC CCAAAGUUGGGGUGCUGGUUUU
hsa-miR-635 ACUUGGGCACUGAAACAAUGUCC ACAUUGUUUCAGUGCCCAAGUUU
hsa-miR-636 UGUGCUUGCUCGUCCCGCCCGCA CGGGCGGGACGAGCAAGCACAUU
hsa-miR-637 ACUGGGGGCUUUCGGGCUCUGCGU GCAGAGCCCGAAAGCCCCCAGUUU
hsa-miR-638 AGGGAUCGCGGGCGGGUGGCGGCCU GCCGCCACCCGCCCGCGAUCCCUUU
hsa-miR-639 AUCGCUGCGGUUGCGAGCGCUGU AGCGCUCGCAACCGCAGCGAUUU
hsa-miR-640 AUGAUCCAGGAACCUGCCUCU AGGCAGGUUCCUGGAUCAUUU
hsa-miR-641 AAAGACAUAGGAUAGAGUCACCUC GGUGACUCUAUCCUAUGUCUUUUU
hsa-miR-642a GUCCCUCUCCAAAUGUGUCUUG AGACACAUUUGGAGAGGGAACC
hsa-miR-642b GGUUCCCUCUCCAAAUGUGUCU AGACACAUUUGGAGAGGGACCC
hsa-miR-643 ACUUGUAUGCUAGCUCAGGUAG ACCUGAGCUAGCAUACAAGUUU
hsa-miR-644a AGUGUGGCUUUCUUAGAGC UCUAAGAAAGCCACACUUU
hsa-miR-645 UCUAGGCUGGUACUGCUGA AGCAGUACCAGCCUAGAUU
hsa-miR-646 AAGCAGCUGCCUCUGAGGC CUCAGAGGCAGCUGCUUUU
hsa-miR-647 GUGGCUGCACUCACUUCCUUC AGGAAGUGAGUGCAGCCACUU
hsa-miR-648 AAGUGUGCAGGGCACUGGU CAGUGCCCUGCACACUUUU
hsa-miR-649 AAACCUGUGUUGUUCAAGAGUC CUCUUGAACAACACAGGUUUUU
hsa-miR-6499 AGCAGUGUUUGUUUUGCCCACA UCGGGCGCAAGAGCACUGCAGU
hsa-miR-650 AGGAGGCAGCGCUCUCAGGAC CCUGAGAGCGCUGCCUCCUUU
hsa-miR-6500 ACACUUGUUGGGAUGACCUGC AGGAGCUAUCCACUCCAGGUGUCC
hsa-miR-6501 CCAGAGCAGCCUGCGGUAACAGU AGUUGCCAGGGCUGCCUUUGGU
hsa-miR-6502 AGCUCUAGAAAGAUUGUUGACC UAGACCAUCUUUCUAGAGUAU
hsa-miR-6503 GGGACUAGGAUGCAGACCUCC AGGUCUGCAUUCAAAUCCCCAGA
hsa-miR-6504 CAUUACAGCACAGCCAUUCU UCUGGCUGUGCUGUAAUGCAG
hsa-miR-6505 UGACUUCUACCUCUUCCAAAG UUGGAAUAGGGGAUAUCUCAGC
hsa-miR-6506 ACUGGGAUGUCACUGAAUAUGGU UCGUAUCAGAGAUUCCAGACAC
hsa-miR-6507 CAAAGUCCUUCCUAUUUUUCCC GAAGAAUAGGAGGGACUUUGU
hsa-miR-6508 UCUAGAAAUGCAUGACCCACC UGGGCCAUGCAUUUCUAGAACU
hsa-miR-6509 AUUAGGUAGUGGCAGUGGAAC UUCCACUGCCACUACCUAAUUU
hsa-miR-651 UUUAGGAUAAGCUUGACUUUUG AAAGGAAAGUGUAUCCUAAAAG
hsa-miR-6510 CAGCAGGGGAGAGAGAGGAGUC CACCGACUCUGUCUCCUGCAG
hsa-miR-6511a CAGGCAGAAGUGGGGCUGACAGG CCUCACCAUCCCUUCUGCCUGC
hsa-miR-6511b CUGCAGGCAGAAGUGGGGCUGACA CCUCACCACCCCUUCUGCCUGCA
hsa-miR-6512 UACCAUUAGAAGAGCUGGAAGA UUCCAGCCCUUCUAAUGGUAGG
hsa-miR-6513 UUUGGGAUUGACGCCACAUGUCU UCAAGUGUCAUCUGUCCCUAG
hsa-miR-6514 CUGCCUGUUCUUCCACUCCAG UAUGGAGUGGACUUUCAGCUGGC
hsa-miR-6515 UCUCUUCAUCUACCCCCCAG UUGGAGGGUGUGGAAGACAUC
hsa-miR-6516 UUUGCAGUAACAGGUGUGAGCA AUCAUGUAUGAUACUGCAAACA
hsa-miR-652 AAUGGCGCCACUAGGGUUGUG CAACCCUAGGAGAGGGUGCCAUUCA
hsa-miR-653 GUGUUGAAACAAUCUCUACUG UUCACUGGAGUUUGUUUCAAUA
hsa-miR-654 UGGUGGGCCGCAGAACAUGUGC UAUGUCUGCUGACCAUCACCUU
hsa-miR-655 AGAGGUUAUCCGUGUUAUGUUC AUAAUACAUGGUUAACCUCUUU
hsa-miR-656 AGGUUGCCUGUGAGGUGUUCA AAUAUUAUACAGUCAACCUCU
hsa-miR-657 GGCAGGUUCUCACCCUCUCUAGG UAGAGAGGGUGAGAACCUGCCUU
hsa-miR-658 GGCGGAGGGAAGUAGGUCCGUUGGU CAACGGACCUACUUCCCUCCGCCUU
hsa-miR-659 AGGACCUUCCCUGAACCAAGGA CUUGGUUCAGGGAGGGUCCCCA
hsa-miR-660 ACCUCCUGUGUGCAUGGAUUA UACCCAUUGCAUAUCGGAGUUG
hsa-miR-661 UGCCUGGGUCUCUGGCCUGCGCGU GCGCAGGCCAGAGACCCAGGCAUU
hsa-miR-662 UCCCACGUUGUGGCCCAGCAG GCUGGGCCACAACGUGGGAUU
hsa-miR-663a AGGCGGGGCGCCGCGGGACCGC GGUCCCGCGGCGCCCCGCCUUU
hsa-miR-663b GGUGGCCCGGCCGUGCCUGAGG UCAGGCACGGCCGGGCCACCUU
hsa-miR-664a ACUGGCUAGGGAAAAUGAUUGGAU UAUUCAUUUAUCCCCAGCCUACA
hsa-miR-664b UUCAUUUGCCUCCCAGCCUACA UGGGCUAAGGGAGAUGAUUGGGUA
hsa-miR-665 ACCAGGAGGCUGAGGCCCCU GGGCCUCAGCCUCCUGGUUU
hsa-miR-668 UGUCACUCGGCUCGGCCCACUAC UGCGCCUCGGGUGAGCAUG
hsa-miR-670 UUUCCUCAUAUUCAUUCAGGA GUCCCUGAGUGUAUGUGGUG
hsa-miR-671 UCCGGUUCUCAGGGCUCCACC AGGAAGCCCUGGAGGGGCUGGAG
hsa-miR-6715a CCAAACCAGUCGUGCCUGUGG ACAGGCACGACUGGUUUGGUU
hsa-miR-6715b CUCAAACCGGCUGUGCCUGUGG ACAGGCACGACUGGUUUGGCA
hsa-miR-6716 UGGGAAUGGGGGUAAGGGCC UCCGAACUCUCCAUUCCUCUGC
hsa-miR-6717 AGGCGAUGUGGGGAUGUAGAGA UCUACAUCCCCACAUCGCCUUU
hsa-miR-6718 UAGUGGUCAGAGGGCUUAUGA AUAAGCCCUCUGACCACUAUU
hsa-miR-6719 UCUGACAUCAGUGAUUCUCCUG GGAGAAUCACUGAUGUCAGAUU
hsa-miR-6720 UUCCAGCCCUGGUAGGCGCCGCG CGCGCCUGCAGGAACUGGUAGA
hsa-miR-6721 UGGGCAGGGGCUUAUUGUAGGAG CCUACAAUAAGCCCCUGCCCAUU
hsa-miR-6722 UGCAGGGGUCGGGUGGGCCAGG AGGCGCACCCGACCACAUGC
hsa-miR-6723 AUAGUCCGAGUAACGUCGGGGC CCCGACGUUACUCGGACUAUUU
hsa-miR-6724 CUGGGCCCGCGGCGGGCGUGGGG CCACGCCCGCCGCGGGCCCAGUU
hsa-miR-6726 CGGGAGCUGGGGUCUGCAGGU CUCGCCCUGUCUCCCGCUAG
hsa-miR-6727 UCCUGCCACCUCCUCCGCAG CUCGGGGCAGGCGGCUGGGAGCG
hsa-miR-6728 UCUCUGCUCUGCUCUCCCCAG UUGGGAUGGUAGGACCAGAGGGG
hsa-miR-6729 UCAUCCCCCUCGCCCUCUCAG UGGGCGAGGGCGGCUGAGCGGC
hsa-miR-6730 AGAAAGGUGGAGGGGUUGUCAGA CCUGACACCCCAUCUGCCCUCA
hsa-miR-6731 UGGGAGAGCAGGGUAUUGUGGA UCUAUUCCCCACUCUCCCCAG
hsa-miR-6732 UAGGGGGUGGCAGGCUGGCC UAACCCUGUCCUCUCCCUCCCAG
hsa-miR-6733 UCAGUGUCUGGAUUUCCUAG UGGGAAAGACAAACUCAGAGUU
hsa-miR-6734 CCCUUCCCUCACUCUUCUCUCAG UUGAGGGGAGAAUGAGGUGGAGA
hsa-miR-6735 AGGCCUGUGGCUCCUCCCUCAG CAGGGCAGAGGGCACAGGAAUCUGA
hsa-miR-6736 UCAGCUCCUCUCUACCCACAG CUGGGUGAGGGCAUCUGUGGU
hsa-miR-6737 UUGGGGUGGUCGGCCCUGGAG UCUGUGCUUCACCCCUACCCAG
hsa-miR-6738 CUUCUGCCUGCAUUCUACUCCCAG CGAGGGGUAGAAGAGCACAGGGG
hsa-miR-6739 AUUGUUCUGUCUUUCUCCCAG UGGGAAAGAGAAAGAACAAGUA
hsa-miR-6740 UGUCUUCUCUCCUCCCAAACAG AGUUUGGGAUGGAGAGAGGAGA
hsa-miR-6741 UCGGCUCUCUCCCUCACCCUAG GUGGGUGCUGGUGGGAGCCGUG
hsa-miR-6742 AGUGGGGUGGGACCCAGCUGUU ACCUGGGUUGUCCCCUCUAG
hsa-miR-6743 AAGGGGCAGGGACGGGUGGCCC AGCCGCUCUUCUCCCUGCCCACA
hsa-miR-6744 GGGCCUCUCUUGUCAUCCUGCAG UGGAUGACAGUGGAGGCCU
hsa-miR-6745 UGGGUGGAAGAAGGUCUGGUU CCAGACCUUCUUCCACCCAUU
hsa-miR-6746 CCGGGAGAAGGAGGUGGCCUGG CAGCCGCCGCCUGUCUCCACAG
hsa-miR-6747 UCCUGCCUUCCUCUGCACCAG AGGGGUGUGGAAAGAGGCAGAACA
hsa-miR-6748 UCCUGUCCCUGUCUCCUACAG UGUGGGUGGGAAGGACUGGAUU
hsa-miR-6749 UCGGGCCUGGGGUUGGGGGAGC CUCCUCCCCUGCCUGGCCCAG
hsa-miR-675 UGGUGCGGAGAGGGCCCACAGUG CUGUAUGCCCUCACCGCUCA
hsa-miR-6750 CAGGGAACAGCUGGGUGAGCUGCU GAACUCACCCUCUGCUCCCAG
hsa-miR-6751 UUGGGGGUGAGGUUGGUGUCUGG ACUGAGCCUCUCUCUCUCCAG
hsa-miR-6752 UCCCUGCCCCCAUACUCCCAG GGGGGGUGUGGAGCCAGGGGGC
hsa-miR-6753 UGGUCUGUCUCUGCCCUGGCAC CACCAGGGCAGAGCAGGGCUGA
hsa-miR-6754 UCUUCACCUGCCUCUGCCUGCA CCAGGGAGGCUGGUUUGGAGGA
hsa-miR-6755 UGUUGUCAUGUUUUUUCCCUAG UAGGGUAGACACUGACAACGUU
hsa-miR-6756 UCCCCUUCCUCCCUGCCCAG AGGGUGGGGCUGGAGGUGGGGCU
hsa-miR-6757 UAGGGAUGGGAGGCCAGGAUGA AACACUGGCCUUGCUAUCCCCA
hsa-miR-6758 ACUCAUUCUCCUCUGUCCAG UAGAGAGGGGAAGGAUGUGAUGU
hsa-miR-6759 UUGUGGGUGGGCAGAAGUCUGU UGACCUUUGCCUCUCCCCUCAG
hsa-miR-676 CUGUCCUAAGGUUGUUGAGUU UCUUCAACCUCAGGACUUGCA
hsa-miR-6760 CAGGGAGAAGGUGGAAGUGCAGA ACACUGUCCCCUUCUCCCCAG
hsa-miR-6761 UCUGAGAGAGCUCGAUGGCAG UCCUACGCUGCUCUCUCACUCC
hsa-miR-6762 CGGGGCCAUGGAGCAGCCUGUGU UGGCUGCUUCCCUUGGUCUCCAG
hsa-miR-6763 CUGGGGAGUGGCUGGGGAG CUCCCCGGCCUCUGCCCCCAG
hsa-miR-6764 UCUCUGGUCUUUCCUUGACAG UCCCAGGGUCUGGUCAGAGUUG
hsa-miR-6765 UCACCUGGCUGGCCCGCCCAG GUGAGGCGGGGCCAGGAGGGUGUGU
hsa-miR-6766 CGGGUGGGAGCAGAUCUUAUUGAG UGAUUGUCUUCCCCCACCCUCA
hsa-miR-6767 UCGCAGACAGGGACACAUGGAGA CCACGUGCUUCUCUUUCCGCAG
hsa-miR-6768 CAAAGGCCACAUUCUCCUGUGCAC CACACAGGAAAAGCGGGGCCCUG
hsa-miR-6769a GAGCCCCUCUCUGCUCUCCAG AGGUGGGUAUGGAGGAGCCCU
hsa-miR-6769b UGGUGGGUGGGGAGGAGAAGUGC CCCUCUCUGUCCCACCCAUAG
hsa-miR-6770 UGAGAAGGCACAGCUUGCACGUGA CUGGCGGCUGUGUCUUCACAG
hsa-miR-6771 CUCGGGAGGGCAUGGGCCAGGC CAAACCCCUGUCUACCCGCAG
hsa-miR-6772 UGGGUGUAGGCUGGAGCUGAGG UUGCUCCUGACUCUGUGCCCACA
hsa-miR-6773 ACUGUCACUUCUCUGCCCAUAG UUGGGCCCAGGAGUAAACAGGAU
hsa-miR-6774 ACUUGGGCAGGAGGGACCCUGUAUG UCGUGUCCCUCUUGUCCACAG
hsa-miR-6775 AGGCCCUGUCCUCUGCCCCAG UCGGGGCAUGGGGGAGGGAGGCUGG
hsa-miR-6776 UCUGGGUGCAGUGGGGGUU CAACCACCACUGUCUCUCCCCAG
hsa-miR-6777 UCCACUCUCCUGGCCCCCAG ACGGGGAGUCAGGCAGUGGUGGA
hsa-miR-6778 UGCCUCCCUGACAUUCCACAG AGUGGGAGGACAGGAGGCAGGU
hsa-miR-6779 AAGCCCUGUCUCCUCCCAUCU CUGGGAGGGGCUGGGUUUGGC
hsa-miR-6780a CUCCUCUGUUUUCUUUCCUAG UUGGGAGGGAAGACAGCUGGAGA
hsa-miR-6780b UCCCUUGUCUCCUUUCCCUAG UGGGGAAGGCUUGGCAGGGAAGA
hsa-miR-6781 CGGGCCGGAGGUCAAGGGCGU UGCCUCUUUUCCACGGCCUCAG
hsa-miR-6782 UAGGGGUGGGGGAAUUCAGGGGUGU CACCUUUGUGUCCCCAUCCUGCA
hsa-miR-6783 UUCCUGGGCUUCUCCUCUGUAG UAGGGGAAAAGUCCUGAUCCGG
hsa-miR-6784 UCUCACCCCAACUCUGCCCCAG GCCGGGGCUUUGGGUGAGGG
hsa-miR-6785 ACAUCGCCCCACCUUCCCCAG UGGGAGGGCGUGGAUGAUGGUG
hsa-miR-6786 UGACGCCCCUUCUGAUUCUGCCU GCGGUGGGGCCGGAGGGGCGU
hsa-miR-6787 UCUCAGCUGCUGCCCUCUCCAG UGGCGGGGGUAGAGCUGGCUGC
hsa-miR-6788 CUGGGAGAAGAGUGGUGAAGA UUCGCCACUUCCCUCCCUGCAG
hsa-miR-6789 CGGCGCCCGUGUCUCCUCCAG GUAGGGGCGUCCCGGGCGCGCGGG
hsa-miR-6790 GUGAGUGUGGAUUUGGCGGGGUU CGACCUCGGCGACCCCUCACU
hsa-miR-6791 CCCCUGGGGCUGGGCAGGCGGA UGCCUCCUUGGUCUCCGGCAG
hsa-miR-6792 CUCCUCCACAGCCCCUGCUCAU GUAAGCAGGGGCUCUGGGUGA
hsa-miR-6793 UGUGGGUUCUGGGUUGGGGUGA UCCCCAACCCCUGCCCGCAG
hsa-miR-6794 CAGGGGGACUGGGGGUGAGC CUCACUCUCAGUCCCUCCCU
hsa-miR-6795 UGGGGGGACAGGAUGAGAGGCUGU ACCCCUCGUUUCUUCCCCCAG
hsa-miR-6796 GAAGCUCUCCCCUCCCCGCAG UUGUGGGGUUGGAGAGCUGGCUG
hsa-miR-6797 UGCAUGACCCUUCCCUCCCCAC AGGAGGGAAGGGGCUGAGAACAGGA
hsa-miR-6798 CCAGGGGGAUGGGCGAGCUUGGG CUACCCCCCAUCCCCCUGUAG
hsa-miR-6799 GGGGAGGUGUGCAGGGCUGG UGCCCUGCAUGGUGUCCCCACAG
hsa-miR-6800 GUAGGUGACAGUCAGGGGCGG CACCUCUCCUGGCAUCGCCCC
hsa-miR-6801 UGGUCAGAGGCAGCAGGAAAUGA ACCCCUGCCACUCACUGGCC
hsa-miR-6802 UUCACCCCUCUCACCUAAGCAG CUAGGUGGGGGGCUUGAAGC
hsa-miR-6803 UCCCUCGCCUUCUCACCCUCAG CUGGGGGUGGGGGGCUGGGCGU
hsa-miR-6804 UGAGGGUGUCAGCAGGUGACG CGCACCUGCCUCUCACCCACAG
hsa-miR-6805 UUGCUCUGCUCCCCCGCCCCCAG UAGGGGGCGGCUUGUGGAGUGU
hsa-miR-6806 UGAAGCUCUGACAUUCCUGCAG UGUAGGCAUGAGGCAGGGCCCAGG
hsa-miR-6807 GUGAGCCAGUGGAAUGGAGAGG CACUGCAUUCCUGCUUGGCCCAG
hsa-miR-6808 CAGGCAGGGAGGUGGGACCAUG GUGUGACCACCGUUCCUGCAG
hsa-miR-6809 CUUCUCUUCUCUCCUUCCCAG UGGCAAGGAAAGAAGAGGAUCA
hsa-miR-6810 AUGGGGACAGGGAUCAGCAUGGC UCCCCUGCUCCCUUGUUCCCCAG
hsa-miR-6811 AGCCUGUGCUUGUCCCUGCAG AUGCAGGCCUGUGUACAGCACU
hsa-miR-6812 AUGGGGUGAGAUGGGGAGGAGCAGC CCGCUCUUCCCCUGACCCCAG
hsa-miR-6813 CAGGGGCUGGGGUUUCAGGUUCU AACCUUGGCCCCUCUCCCCAG
hsa-miR-6814 ACUCGCAUCCUUCCCUUGGCAG UCCCAAGGGUGAGAUGCUGCCA
hsa-miR-6815 UAGGUGGCGCCGGAGGAGUCAUU UGGCUUCUCUUGCACACCCAG
hsa-miR-6816 UGGGGCGGGGCAGGUCCCUGC GAAGGACCUGCACCUUCG
hsa-miR-6817 UCUGCCAUAGGAAGCUUGGAGUGG UCUCUCUGACUCCAUGGCA
hsa-miR-6818 UUGUGUGAGUACAGAGAGCAUC UUGUCUCUUGUUCCUCACACAG
hsa-miR-6819 UUGGGGUGGAGGGCCAAGGAGC AAGCCUCUGUCCCCACCCCAG
hsa-miR-6820 UGCGGCAGAGCUGGGGUCA UGUGACUUCUCCCCUGCCACAG
hsa-miR-6821 GUGCGUGGUGGCUCGAGGCGGGG UGACCUCUCCGCUCCGCACAG
hsa-miR-6822 AGGCUCUAACUGGCUUUCCCUGCA CAGGGAACCAGUUGGGGCUU
hsa-miR-6823 UCAGGGUUGGUAGGGGUUGCU UGAGCCUCUCCUUCCCUCCAG
hsa-miR-6824 GUAGGGGAGGUUGGGCCAGGGA UCUCUGGUCUUGCCACCCCAG
hsa-miR-6825 GCGCUGACCCGCCUUCUCCGCA UGGGGAGGUGUGGAGUCAGCAU
hsa-miR-6826 CUCCCCUCUCUUUCCUGUUCAG UCAAUAGGAAAGAGGUGGGACCU
hsa-miR-6827 UGGGAGCCAUGAGGGUCUGUGC ACCGUCUCUUCUGUUCCCCAG
hsa-miR-6828 AUCUGCUCUCUUGUUCCCAG AGGAAGCAAGAGAACCCUGUGG
hsa-miR-6829 UGGGCUGCUGAGAAGGGGCA UGCCUCCUCCGUGGCCUCAG
hsa-miR-6830 CCAAGGAAGGAGGCUGGACAUC UGUCUUUCUUCUCUCCCUUGCAG
hsa-miR-6831 UAGGUAGAGUGUGAGGAGGAGGUC UGACUAACUCCCACUCUACAG
hsa-miR-6832 AGUAGAGAGGAAAAGUUAGGGUC ACCCUUUUUCUCUUUCCCAG
hsa-miR-6833 UUUCUCUCUCCACUUCCUCAG GUGUGGAAGAUGGGAGGAGAAA
hsa-miR-6834 GUGAGGGACUGGGAUUUGUGG UAUGUCCCAUCCCUCCAUCA
hsa-miR-6835 AGGGGGUAGAAAGUGGCUGAAG AAAAGCACUUUUCUGUCUCCCAG
hsa-miR-6836 AUGCCUCCCCCGGCCCCGCAG CGCAGGGCCCUGGCGCAGGCAU
hsa-miR-6837 ACCAGGGCCAGCAGGGAAUGU CCUUCACUGUGACUCUGCUGCAG
hsa-miR-6838 AAGCAGCAGUGGCAAGACUCCU AAGUCCUGCUUCUGUUGCAG
hsa-miR-6839 UCUGGAUUGAAGAGACGACCCA UUGGGUUUUCUCUUCAAUCCAG
hsa-miR-6840 ACCCCCGGGCAAAGACCUGCAGAU GCCCAGGACUUUGUGCGGGGUG
hsa-miR-6841 UAGGGUACUCAGAGCAAGUUGU ACCUUGCAUCUGCAUCCCCAG
hsa-miR-6842 UGGGGGUGGUCUCUAGCCAAGG UUGGCUGGUCUCUGCUCCGCAG
hsa-miR-6843 AUGGUCUCCUGUUCUCUGCAG GCAGAGAACAGGAGACCAUUU
hsa-miR-6844 UUCUUUGUUUUUAAUUCACAG GUGAAUUAAAAACAAAGAAUU
hsa-miR-6845 CGGGGCCAGAGCAGAGAGC CCUCUCCUCCCUGUGCCCCAG
hsa-miR-6846 UGACCCCUUCUGUCUCCCUAG UGGGGGCUGGAUGGGGUAGAGU
hsa-miR-6847 GGCUCAUGUGUCUGUCCUCUUC ACAGAGGACAGUGGAGUGUGAGC
hsa-miR-6848 UGGGGGCUGGGAUGGGCCAUGGU GUGGUCUCUUGGCCCCCAG
hsa-miR-6849 ACCAGCCUGUGUCCACCUCCAG GAGUGGAUAGGGGAGUGUGUGGA
hsa-miR-6850 CCCGGCCGGAACGCCGCACU GUGCGGAACGCUGGCCGGGGCG
hsa-miR-6851 AGGAGGUGGUACUAGGGGCCAGC UGGCCCUUUGUACCCCUCCAG
hsa-miR-6852 CCCUGGGGUUCUGAGGACAUG UGUCCUCUGUUCCUCAG
hsa-miR-6853 AGCGUGGGAUGUCCAUGAAGUCAG UGUUCAUUGGAACCCUGCGCAG
hsa-miR-6854 UGCGUUUCUCCUCUUGAGCAG AAGCUCAGGUUUGAGAACUGCUGA
hsa-miR-6855 AGACUGACCUUCAACCCCACAG UUGGGGUUUGGGGUGCAGACAUUGC
hsa-miR-6856 UACAGCCCUGUGAUCUUUCCAG AAGAGAGGAGCAGUGGUGCUGUGG
hsa-miR-6857 UGACUGAGCUUCUCCCCACAG UUGGGGAUUGGGUCAGGCCAGU
hsa-miR-6858 CAGCCAGCCCCUGCUCACCCCU GUGAGGAGGGGCUGGCAGGGAC
hsa-miR-6859 UGACCCCCAUGUCGCCUCUGUAG GAGAGGAACAUGGGCUCAGGACA
hsa-miR-6860 ACUGGGCAGGGCUGUGGUGAGU UCACCACAGCCCUGCCCAGUUU
hsa-miR-6861 ACUGGGUAGGUGGGGCUCCAGG UGGACCUCUCCUCCCCAG
hsa-miR-6862 CCUCACCCAGCUCUCUGGCCCUCU CGGGCAUGCUGGGAGAGACUUU
hsa-miR-6863 UAGACGUGGUGAAGGAUUGAGUG CUCAAUCCUUCACCACGUCUAUU
hsa-miR-6864 UUGAAGGGACAAGUCAGAUAUGCC GUGAGACUUCUCUCCCUUCAG
hsa-miR-6865 ACACCCUCUUUCCCUACCGCC UAGGUGGCAGAGGAGGGACUUCA
hsa-miR-6866 GAUCCCUUUAUCUGUCCUCUAG UUAGAGGCUGGAAUAGAGAUUCU
hsa-miR-6867 UGUGUGUGUAGAGGAAGAAGGGA CUCUCCCUCUUUACCCACUAG
hsa-miR-6868 ACUGGCAGAACACUGAAGCAGC UUCCUUCUGUUGUCUGUGCAG
hsa-miR-6869 GUGAGUAGUGGCGCGCGGCGGC CGCCGCGCGCAUCGGCUCAGC
hsa-miR-6870 UGGGGGAGAUGGGGGUUGA GCUCAUCCCCAUCUCCUUUCAG
hsa-miR-6871 CAUGGGAGUUCGGGGUGGUUGC CAGCACCCUGUGGCUCCCACAG
hsa-miR-6872 CCCAUGCCUCCUGCCGCGGUC UCUCGCAUCAGGAGGCAAGG
hsa-miR-6873 UUCUCUCUGUCUUUCUCUCUCAG CAGAGGGAAUACAGAGGGCAAU
hsa-miR-6874 AUGGAGCUGGAACCAGAUCAGGC CAGUUCUGCUGUUCUGACUCUAG
hsa-miR-6875 UGAGGGACCCAGGACAGGAGA AUUCUUCCUGCCCUGGCUCCAU
hsa-miR-6876 AGCUGUCUGUGUUUUCCUUCUCAG CAGGAAGGAGACAGGCAGUUCA
hsa-miR-6877 CAGCCUCUGCCCUUGGCCUCC AGGGCCGAAGGGUGGAAGCUGC
hsa-miR-6878 CUGGCCUCUUCUUUCUCCUAG AGGGAGAAAGCUAGAAGCUGAAG
hsa-miR-6879 UGUCACCCGCUCCUUGCCCAG CAGGGCAGGGAAGGUGGGAGAG
hsa-miR-6880 UGGUGGAGGAAGAGGGCAGCUC CCGCCUUCUCUCCUCCCCCAG
hsa-miR-6881 AUCCUCUUUCGUCCUUCCCACU UGGGGUAAGGAUAGGAGGGUCA
hsa-miR-6882 UGCUGCCUCUCCUCUUGCCUGCAG UACAAGUCAGGAGCUGAAGCAG
hsa-miR-6883 UUCCCUAUCUCACUCUCCUCAG AGGGAGGGUGUGGUAUGGAUGU
hsa-miR-6884 CCCAUCACCUUUCCGUCUCCCCU AGAGGCUGAGAAGGUGAUGUUG
hsa-miR-6885 AGGGGGGCACUGCGCAAGCAAAGCC CUUUGCUUCCUGCUCCCCUAG
hsa-miR-6886 UGCCCUUCUCUCCUCCUGCCU CCCGCAGGUGAGAUGAGGGCU
hsa-miR-6887 UCCCCUCCACUUUCCUCCUAG UGGGGGGACAGAUGGAGAGGACA
hsa-miR-6888 AAGGAGAUGCUCAGGCAGAU AUCUGUCUCGAUUGUUUCCAG
hsa-miR-6889 UCGGGGAGUCUGGGGUCCGGAAU UCUGUGCCCCUACUUCCCAG
hsa-miR-6890 CCACUGCCUAUGCCCCACAG CAUGGGGUAGGGCAGAGUAGG
hsa-miR-6891 CCCUCAUCUUCCCCUCCUUUC UAAGGAGGGGGAUGAGGGG
hsa-miR-6892 GUAAGGGACCGGAGAGUAGGA UCCCUCUCCCACCCCUUGCAG
hsa-miR-6893 CCCUGCUGCCUUCACCUGCCAG CAGGCAGGUGUAGGGUGGAGC
hsa-miR-6894 UUGCCUGCCCUCUUCCUCCAG AGGAGGAUGGAGAGCUGGGCCAGA
hsa-miR-6895 CAGGGCCAGGCACAGAGUAAG UGUCUCUCGCCCUUGGCCUUAG
hsa-miR-7-1 UGGAAGACUAGUGAUUUUGUUGU CAACAAAUCACAGUCUGCCAUA
hsa-miR-7-2 UGGAAGACUAGUGAUUUUGUUGU CAACAAAUCCCAGUCUACCUAA
hsa-miR-708 CAACUAGACUGUGAGCUUCUAG AAGGAGCUUACAAUCUAGCUGGG
hsa-miR-7106 UGGGAGGAGGGGAUCUUGGG AGCUCCCUGAAUCCCUGUCCCAG
hsa-miR-7107 UCGGCCUGGGGAGGAGGAAGGG UGGUCUGUUCAUUCUCUCUUUUUGGCC
hsa-miR-7108 GUGUGGCCGGCAGGCGGGUGG ACCCGCCCGUCUCCCCACAG
hsa-miR-7109 CAAGCCUCUCCUGCCCUUCCAG CUGGGGGGAGGAGACCCUGCU
hsa-miR-711 GGGACCCAGGGAGAGACGUAAG UACGUCUCUCCCUGGGUCCCUU
hsa-miR-7110 UCUCUCUCCCACUUCCCUGCAG UGGGGGUGUGGGGAGAGAGAG
hsa-miR-7111 AUCCUCUCUUCCCUCCUCCCAG UGGGGGAGGAAGGACAGGCCAU
hsa-miR-7112 UGCAUCACAGCCUUUGGCCCUAG ACGGGCAGGGCAGUGCACCCUG
hsa-miR-7113 UCCAGGGAGACAGUGUGUGAG CCUCCCUGCCCGCCUCUCUGCAG
hsa-miR-7114 UGACCCACCCCUCUCCACCAG UCUGUGGAGUGGGGUGCCUGU
hsa-miR-7150 CUGGCAGGGGGAGAGGUA CCUCUCCCCCUGCCAGUU
hsa-miR-7151 GAUCCAUCUCUGCCUGUAUUGGC CUACAGGCUGGAAUGGGCUCA
hsa-miR-7152 UCUGGUCCUGGACAGGAGGC UUUCCUGUCCUCCAACCAGACC
hsa-miR-7153 CACCAUGGACGGUUUACC UGAGAACUGACAAAUGUGGUAGG
hsa-miR-7154 UUCAUGAACUGGGUCUAGCUUGG AGGAGGACAAGUUGUGGGAU
hsa-miR-7155 UGGCCCAAGACCUCAGACC UCUGGGGUCUUGGGCCAUC
hsa-miR-7156 CUGCAGCCACUUGGGGAACUGGU UUGUUCUCAAACUGGCUGUCAGA
hsa-miR-7157 UCUGUGCUACUGGAUGAAGAGU UCAGCAUUCAUUGGCACCAGAGA
hsa-miR-7158 GGCUCAAUCUCUGGUCCUGCAGCC CUGAACUAGAGAUUGGGCCCA
hsa-miR-7159 UUUCUAUGUUAGUUGGAAG UUCAACAAGGGUGUAGGAUGG
hsa-miR-7160 CAGGGCCCUGGCUUUAGCAGA UGCUGAGGUCCGGGCUGUGCC
hsa-miR-7161 UAAAGACUGUAGAGGCAACUGGU UAGAUCUUUGACUCUGGCAGUCUCCAGG
hsa-miR-7162 UCUGAGGUGGAACAGCAGC UGCUUCCUUUCUCAGCUG
hsa-miR-718 CUUCCGCCCCGCCGGGCGUCG ACGCCCGGCGGGGCGGAAGUU
hsa-miR-744 UGCGGGGCUAGGGCUAACAGCA CUGUUGCCACUAACCUCAACCU
hsa-miR-7515 AGAAGGGAAGAUGGUGAC CACCAUCUUCCCUUCUUU
hsa-miR-758 UUUGUGACCUGGUCCACUAACC GAUGGUUGACCAGAGAGCACAC
hsa-miR-759 GCAGAGUGCAAACAAUUUUGAC CAAAAUUGUUUGCACUCUGCUU
hsa-miR-760 CGGCUCUGGGUCUGUGGGGA CCCACAGACCCAGAGCCGUU
hsa-miR-761 GCAGCAGGGUGAAACUGACACA UGUCAGUUUCACCCUGCUGCUU
hsa-miR-762 GGGGCUGGGGCCGGGGCCGAGC UCGGCCCCGGCCCCAGCCCCUU
hsa-miR-764 GCAGGUGCUCACUUGUCCUCCU GAGGACAAGUGAGCACCUGCUU
hsa-miR-7641 UUGAUCUCGGAAGCUAAGC UUAGCUUCCGAGAUCAAUU
hsa-miR-765 UGGAGGAGAAGGAAGGUGAUG UCACCUUCCUUCUCCUCCAUU
hsa-miR-766 AGGAGGAAUUGGUGCUGGUCUU ACUCCAGCCCCACAGCCUCAGC
hsa-miR-767 UGCACCAUGGUUGUCUGAGCAUG UCUGCUCAUACCCCAUGGUUUCU
hsa-miR-769 CUGGGAUCUCCGGGGUCUUGGUU UGAGACCUCUGGGUUCUGAGCU
hsa-miR-770 UCCAGUACCACGUGUCAGGGCCA GCCCUGACACGUGGUACUGGAUU
hsa-miR-7702 CUUAGACUGCCAGACUCCCUGA AGGGAGUCUGGCAGUCUAAGUU
hsa-miR-7703 UUGCACUCUGGCCUUCUCCCAGG UGGGAGAAGGCCAGAGUGCAAUU
hsa-miR-7704 CGGGGUCGGCGGCGACGUG CGUCGCCGCCGACCCCGUU
hsa-miR-7705 AAUAGCUCAGAAUGUCAGUUCUG GAACUGACAUUCUGAGCUAUUUU
hsa-miR-7706 UGAAGCGCCUGUGCUCUGCCGAGA UCGGCAGAGCACAGGCGCUUCAUU
hsa-miR-7843 AUGAAGCCUUCUCUGCCUUACG GAGGGCAGAGCCAGCUUCCUGA
hsa-miR-7844 AAAACUAGGACUGUGUGGUGUA CACCACACAGUCCUAGUUUUUU
hsa-miR-7845 AAGGGACAGGGAGGGUCGUGG ACGACCCUCCCUGUCCCUUUU
hsa-miR-7846 CAGCGGAGCCUGGAGAGAAGG UUCUCUCCAGGCUCCGCUGUU
hsa-miR-7847 CGUGGAGGACGAGGAGGAGGC CUCCUCCUCGUCCUCCACGUU
hsa-miR-7848 CUACCCUCGGUCUGCUUACCACA UGGUAAGCAGACCGAGGGUAGUU
hsa-miR-7849 GACAAUUGUUGAUCUUGGGCCU GCCCAAGAUCAACAAUUGUCUU
hsa-miR-7850 GUUUGGACAUAGUGUGGCUGG AGCCACACUAUGUCCAAACUU
hsa-miR-7851 UACCUGGGAGACUGAGGUUGGA CAACCUCAGUCUCCCAGGUAUU
hsa-miR-7852 UAUGUAGUAGUCAAAGGCAUUU AUGCCUUUGACUACUACAUAUU
hsa-miR-7853 UCAAAUGCAGAUCCUGACUUC AGUCAGGAUCUGCAUUUGAUU
hsa-miR-7854 UGAGGUGACCGCAGAUGGGAA CCCAUCUGCGGUCACCUCAUU
hsa-miR-7855 UUGGUGAGGACCCCAAGCUCGG GAGCUUGGGGUCCUCACCAAUU
hsa-miR-7856 UUUUAAGGACACUGAGGGAUC UCCCUCAGUGUCCUUAAAAUU
hsa-miR-7973 UGUGACCCUAGAAUAAUUAC AAUUAUUCUAGGGUCACAUU
hsa-miR-7974 AGGCUGUGAUGCUCUCCUGAGCCC GCUCAGGAGAGCAUCACAGCCUUU
hsa-miR-7975 AUCCUAGUCACGGCACCA GUGCCGUGACUAGGAUUU
hsa-miR-7976 UGCCCUGAGACUUUUGCUC GCAAAAGUCUCAGGGCAUU
hsa-miR-7977 UUCCCAGCCAACGCACCA GUGCGUUGGCUGGGAAUU
hsa-miR-7978 UCUGGUGUAUAGCGUUGCUCA AGCAACGCUAUACACCAGAUU
hsa-miR-802 CAGUAACAAAGAUUCAUCCUUGU AAGGAUGAAUCUUUGUUACUGUU
hsa-miR-8052 CGGGACUGUAGAGGGCAUGAGC UCAUGCCCUCUACAGUCCCGUU
hsa-miR-8053 UGGCGAUUUUGGAACUCAAUGGCA CCAUUGAGUUCCAAAAUCGCCAUU
hsa-miR-8054 GAAAGUACAGAUCGGAUGGGU CCAUCCGAUCUGUACUUUCUU
hsa-miR-8055 CUUUGAGCACAUGAGCAGACGGA CGUCUGCUCAUGUGCUCAAAGUU
hsa-miR-8056 CGUGGAUUGUCUGGAUGCAU GCAUCCAGACAAUCCACGUU
hsa-miR-8057 GUGGCUCUGUAGUAAGAUGGA CAUCUUACUACAGAGCCACUU
hsa-miR-8058 CUGGACUUUGAUCUUGCCAUAA AUGGCAAGAUCAAAGUCCAGUU
hsa-miR-8059 GGGGAACUGUAGAUGAAAAGGC CUUUUCAUCUACAGUUCCCCUU
hsa-miR-8060 CCAUGAAGCAGUGGGUAGGAGGAC CCUCCUACCCACUGCUUCAUGGUU
hsa-miR-8061 CUUAGAUUAGAGGAUAUUGUU CAAUAUCCUCUAAUCUAAGUU
hsa-miR-8062 CAGUGAUUUGAGGAUUAUUGC AAUAAUCCUCAAAUCACUGUU
hsa-miR-8063 UCAAAAUCAGGAGUCGGGGCUU GCCCCGACUCCUGAUUUUGAUU
hsa-miR-8064 AGCACACUGAGCGAGCGGAC CCGCUCGCUCAGUGUGCUUU
hsa-miR-8065 UGUAGGAACAGUUGAAUUUUGGCU CCAAAAUUCAACUGUUCCUACAUU
hsa-miR-8066 CAAUGUGAUCUUUUGGAUGUA CAUCCAAAAGAUCACAUUGUU
hsa-miR-8067 CCUAGAAACUGUAAACUUAGUC CUAAGUUUACAGUUUCUAGGUU
hsa-miR-8068 UGUUUGUUGUAAGGAUCGUUGU AACGAUCCUUACAACAAACAUU
hsa-miR-8069 GGAUGGUUGGGGGCGGUCGGCGU GCCGACCGCCCCCAACCAUCCUU
hsa-miR-8070 AUGUGAUUGACGGCUGACUCCA GAGUCAGCCGUCAAUCACAUUU
hsa-miR-8071 CGGUGGACUGGAGUGGGUGG ACCCACUCCAGUCCACCGUU
hsa-miR-8072 GGCGGCGGGGAGGUAGGCAG GCCUACCUCCCCGCCGCCUU
hsa-miR-8073 ACCUGGCAGCAGGGAGCGUCGU GACGCUCCCUGCUGCCAGGUUU
hsa-miR-8074 CUAUGGCGAGACUGGCAUGUACUC GUACAUGCCAGUCUCGCCAUAGUU
hsa-miR-8075 UGCUGAUGGCAGAUGUCGGGUCUG GACCCGACAUCUGCCAUCAGCAUU
hsa-miR-8076 UAUAUGGACUUUUCUGAUACAAUG UUGUAUCAGAAAAGUCCAUAUAUU
hsa-miR-8077 GGCUGAGUGGGGUUCUGACUCC AGUCAGAACCCCACUCAGCCUU
hsa-miR-8078 GGUCUAGGCCCGGUGAGAGACUC GUCUCUCACCGGGCCUAGACCUU
hsa-miR-8079 CAGUGAUCGUCUCUGCUGGC CAGCAGAGACGAUCACUGUU
hsa-miR-8080 GAAGGACACUGGUGUCAACGGCU CCGUUGACACCAGUGUCCUUCUU
hsa-miR-8081 CUUGAGUCGUGCCUUUCUGAAUG UUCAGAAAGGCACGACUCAAGUU
hsa-miR-8082 UGAUGGAGCUGGGAAUACUCUG GAGUAUUCCCAGCUCCAUCAUU
hsa-miR-8083 CAGGACUUGACGGCUGCAACU UUGCAGCCGUCAAGUCCUGUU
hsa-miR-8084 GAAUACUAAGUAAAAAAUCAGUA CUGAUUUUUUACUUAGUAUUCUU
hsa-miR-8085 UGGGAGAGAGGACUGUGAGGC CUCACAGUCCUCUCUCCCAUU
hsa-miR-8086 UGCUAGUCUGGACUGAUAUGGU CAUAUCAGUCCAGACUAGCAUU
hsa-miR-8087 GAAGACUUCUUGGAUUACAGGGG CCUGUAAUCCAAGAAGUCUUCUU
hsa-miR-8088 CCUCGGUACUGGAAAGGGGUA CCCCUUUCCAGUACCGAGGUU
hsa-miR-8089 CCUGGGGACAGGGGAUUGGGGCAG GCCCCAAUCCCCUGUCCCCAGGUU
hsa-miR-8485 CACACACACACACACACGUAU ACGUGUGUGUGUGUGUGUGUU
hsa-miR-873 GCAGGAACUUGUGAGUCUCCU GGAGACUGAUGAGUUCCCGGGA
hsa-miR-874 CGGCCCCACGCACCAGGGUAAGA CUGCCCUGGCCCGAGGGACCGA
hsa-miR-875 UAUACCUCAGUUUUAUCAGGUG CCUGGAAACACUGAGGUUGUG
hsa-miR-876 UGGAUUUCUUUGUGAAUCACCA UGGUGGUUUACAAAGUAAUUCA
hsa-miR-877 UCCUCUUCUCCCUCCUCCCAG GUAGAGGAGAUGGCGCAGGG
hsa-miR-885 UCCAUUACACUACCCUGCCUCU AGGCAGCGGGGUGUAGUGGAUA
hsa-miR-887 CUUGGGAGCCCUGUUAGACUC GUGAACGGGCGCCAUCCCGAGG
hsa-miR-888 UACUCAAAAAGCUGUCAGUCA GACUGACACCUCUUUGGGUGAA
hsa-miR-889 AAUGGCUGUCCGUAGUAUGGUC UUAAUAUCGGACAACCAUUGU
hsa-miR-890 UACUUGGAAAGGCAUCAGUUG ACUGAUGCCUUUCCAAGUAUU
hsa-miR-891a AGUGGCACAUGUUUGUUGUGAG UGCAACGAACCUGAGCCACUGA
hsa-miR-891b UGCAACUUACCUGAGUCAUUGA AAUGACUCAGGUAAGUUGCAUU
hsa-miR-892a CACUGUGUCCUUUCUGCGUAG ACGCAGAAAGGACACAGUGUU
hsa-miR-892b CACUGGCUCCUUUCUGGGUAGA UACCCAGAAAGGAGCCAGUGUU
hsa-miR-892c CACUGUUUCCUUUCUGAGUGGA UAUUCAGAAAGGUGCCAGUCA
hsa-miR-9 UCUUUGGUUAUCUAGCUGUAUGA AUAAAGCUAGAUAACCGAAAGU
hsa-miR-920 GGGGAGCUGUGGAAGCAGUA CUGCUUCCACAGCUCCCCUU
hsa-miR-921 CUAGUGAGGGACAGAACCAGGAUUC AUCCUGGUUCUGUCCCUCACUAGUU
hsa-miR-922 GCAGCAGAGAAUAGGACUACGUC CGUAGUCCUAUUCUCUGCUGCUU
hsa-miR-924 AGAGUCUUGUGAUGUCUUGC AAGACAUCACAAGACUCUUU
hsa-miR-92a-1 UAUUGCACUUGUCCCGGCCUGU AGGUUGGGAUCGGUUGCAAUGCU
hsa-miR-92a-2 UAUUGCACUUGUCCCGGCCUGU GGGUGGGGAUUUGUUGCAUUAC
hsa-miR-92b UAUUGCACUCGUCCCGGCCUCC AGGGACGGGACGCGGUGCAGUG
hsa-miR-93 ACUGCUGAGCUAGCACUUCCCG CAAAGUGCUGUUCGUGCAGGUAG
hsa-miR-933 UGUGCGCAGGGAGACCUCUCCC GAGAGGUCUCCCUGCGCACAUU
hsa-miR-934 UGUCUACUACUGGAGACACUGG AGUGUCUCCAGUAGUAGACAUU
hsa-miR-935 CCAGUUACCGCUUCCGCUACCGC GGUAGCGGAAGCGGUAACUGGUU
hsa-miR-936 ACAGUAGAGGGAGGAAUCGCAG GCGAUUCCUCCCUCUACUGUUU
hsa-miR-937 AUCCGCGCUCUGACUCUCUGCC GUGAGUCAGGGUGGGGCUGG
hsa-miR-938 UGCCCUUAAAGGUGAACCCAGU UGGGUUCACCUUUAAGGGCAUU
hsa-miR-939 CCCUGGGCCUCUGCUCCCCAG UGGGGAGCUGAGGCUCUGGGGGUG
hsa-miR-940 AAGGCAGGGCCCCCGCUCCCC GGAGCGGGGGCCCUGCCUUUU
hsa-miR-941 CACCCGGCUGUGUGCACAUGUGC ACAUGUGCACACAGCCGGGUGUU
hsa-miR-942 UCUUCUCUGUUUUGGCCAUGUG CACAUGGCCGAAACAGAGAAGU
hsa-miR-943 CUGACUGUUGCCGUCCUCCAG GGAGGACGGCAACAGUCAGUU
hsa-miR-944 AAAUUAUUGUACAUCGGAUGAG CAUCCGAUGUACAAUAAUUUUU
hsa-miR-95 UCAAUAAAUGUCUGUUGAAUU UUCAACGGGUAUUUAUUGAGCA
hsa-miR-9500 AAGGGAAGAUGGUGACCAC GGUCACCAUCUUCCCUUUU
hsa-miR-96 UUUGGCACUAGCACAUUUUUGCU AAUCAUGUGCAGUGCCAAUAUG
hsa-miR-98 CUAUACAACUUACUACUUUCCC UGAGGUAGUAAGUUGUAUUGUU
hsa-miR-99a CAAGCUCGCUUCUAUGGGUCUG AACCCGUAGAUCCGAUCUUGUG
hsa-miR-99b CACCCGUAGAACCGACCUUGCG CAAGCUCGUGUCUGUGGGUCCG
실시예 2: miRNA 라이브러리 표본의 활성 측정
실시예 1에서 합성한 miRNA 이중 가닥의 활성 여부를 측정하기 위하여 1700 여종의 miRNA 스크리닝 라이브러리로부터 선별적으로 miR-34a, miR-100, miR-125b 를 선택하였다. 선별된 miRNA 는 기 수행된 많은 연구로부터 기능 및 발현을 제어하는 목표 mRNA 종류 및 각 mRNA 3'UTR 에 결합하는 결합 구역 등에 관한 연구가 많이 진행되어 있는 관계로 선택하였다. miR-34a, miR-100, miR-125b 각각에 의하여 발현이 제어되는 것으로 널리 알려진 Bcl2, mTOR, Lin28b mRNA 의 3' UTR 부분을 파이어플라이 루시퍼아제 벡터 (firefly luciferase vector) 의 3' UTR 에 치환하여 각 miRNA 에 상응하는 벡터를 제작하였다. 각 벡터와 miR 대조군, 또는 각 벡터에 상응하는 miR-34a, miR-100, miR-125b 를 올리고의 세포 내 전달 시약인 리포펙타민 2000(Lipofectamine 2000, Invitrogen)을 사용하여 HEK-293T 세포주에 co-transfection 하고 (세 반복 시료 제작), 37°C, 5% (v/v) 이산화탄소 조건에서 24 시간 배양하였다. 루시퍼아제의 활성은 Luminometer(Thermo scientific)를 사용하여 측정하여 합성된 miRNA의 활성을 확인하였다(도 1).
실시예 3: 폐암 세포주의 증식 억제 유발 마이크로 RNA 발굴을 위한 스크리닝
96-well plate 에 3,000 - 10,000 개의 NCI-H460 세포주를 분주하여 24시간 동안 37°C, 5% (v/v) 이산화탄소 조건에서 배양한 후, miRNA 라이브러리의 각 miRNA 를 RNAiMAX 시약(Invitrogen)을 사용하여 최종 농도가 100nM 이 되도록 transfection을 진행하였다. 각 miRNA는 3회 반복하여 transfection을 진행하였기 때문에, 96-well plate에 보관된 miRNA 라이브러리 한 개의 plate 당 세 개의 실험 96-well plate를 준비한 것이다. 이를 상기 세포 배양 조건과 동일한 조건에서 24시간 더 배양한 후 레사주린 (Resazurin) 시약(Promega)을 첨가하여 발생하는 형광 값을 형광 측정기 (Fluoremeter, Tecan)를 사용하여 측정하였다. 각 miRNA에 의한 세포 증식 억제 능력을 상대적으로 비교 평가 하기 위하여, 96-well plate에서 측정된 96개 값의 평균값과 표준 편차를 구하고, 평균값으로부터 각 miRNA가 포함된 well 에서의 측정값이 몇 표준 편차 배수만큼 떨어져 있는지를 (Z-score) 아래의 공식에 대입하여 계산하였다.
Figure 112016018567626-pat00001
이 때, xi 는 각 well 의 측정값이고, μ는 plate 의 전체 well 측정값의 평균값이고, σ는 표준 편차이다. 각 well의 표준 편차 배수 zi는 3회 반복 plate에서 얻어진 평균값으로 이를 통하여 z 값이 -2 보다 작은 값을 보이는 50 여개의 1차 후보 miRNA를 선정하였다(도 2, 표 2).
1차 선별 miRNA 서열
서열번호 1 hsa-miR-23c 가닥 1 AUCACAUUGCCAGUGAUUACCC
서열번호 2 hsa-miR-23c 가닥 2 GUAAUCACUGGCAAUGUGAUUU
서열번호 3 hsa-miR-219b 가닥 1 AGAUGUCCAGCCACAAUUCUCG
서열번호 4 hsa-miR-219b 가닥 2 AGAAUUGCGUUUGGACAAUCAGU
서열번호 5 hsa-miR-378c 가닥 1 ACUGGACUUGGAGUCAGAAGAGUGG
서열번호 6 hsa-miR-378c 가닥 2 ACUCUUCUGACUCCAAGUCCAGUUU
서열번호 7 hsa-miR-548aa 가닥 1 AAAAACCACAAUUACUUUUGCACCA
서열번호 8 hsa-miR-548aa 가닥 2 GUGCAAAAGUAAUUGUGGUUUUUUU
서열번호 9 hsa-miR-548u 가닥 1 CAAAGACUGCAAUUACUUUUGCG
서열번호 10 hsa-miR-548u 가닥 2 CAAAAGUAAUUGCAGUCUUUGUU
서열번호 11 hsa-miR-571 가닥 1 UGAGUUGGCCAUCUGAGUGAG
서열번호 12 hsa-miR-571 가닥 2 CACUCAGAUGGCCAACUCAUU
서열번호 13 hsa-miR-641 가닥 1 AAAGACAUAGGAUAGAGUCACCUC
서열번호 14 hsa-miR-641 가닥 2 GGUGACUCUAUCCUAUGUCUUUUU
서열번호 15 hsa-miR-1244 가닥 1 AAGUAGUUGGUUUGUAUGAGAUGGUU
서열번호 16 hsa-miR-1244 가닥 2 CCAUCUCAUACAAACCAACUACUUUU
서열번호 17 hsa-miR-1248 가닥 1 ACCUUCUUGUAUAAGCACUGUGCUAAA
서열번호 18 hsa-miR-1248 가닥 2 UAGCACAGUGCUUAUACAAGAAGGUUU
서열번호 19 hsa-miR-1298 가닥 1 CAUCUGGGCAACUGACUGAAC
서열번호 20 hsa-miR-1298 가닥 2 UUCAUUCGGCUGUCCAGAUGUA
서열번호 21 hsa-miR-2392 가닥 1 UAGGAUGGGGGUGAGAGGUG
서열번호 22 hsa-miR-2392 가닥 2 CCUCUCACCCCCAUCCUAUU
서열번호 23 hsa-miR-3119 가닥 1 UGGCUUUUAACUUUGAUGGC
서열번호 24 hsa-miR-3119 가닥 2 CAUCAAAGUUAAAAGCCAUU
서열번호 25 hsa-miR-3164 가닥 1 UGUGACUUUAAGGGAAAUGGCG
서열번호 26 hsa-miR-3164 가닥 2 CCAUUUCCCUUAAAGUCACAUU
서열번호 27 hsa-miR-3188 가닥 1 AGAGGCUUUGUGCGGAUACGGGG
서열번호 28 hsa-miR-3188 가닥 2 CCGUAUCCGCACAAAGCCUCUUU
서열번호 29 hsa-miR-3609 가닥 1 CAAAGUGAUGAGUAAUACUGGCUG
서열번호 30 hsa-miR-3609 가닥 2 GCCAGUAUUACUCAUCACUUUGUU
서열번호 31 hsa-miR-3612 가닥 1 AGGAGGCAUCUUGAGAAAUGGA
서열번호 32 hsa-miR-3612 가닥 2 CAUUUCUCAAGAUGCCUCCUUU
서열번호 33 hsa-miR-3662 가닥 1 GAAAAUGAUGAGUAGUGACUGAUG
서열번호 34 hsa-miR-3662 가닥 2 UCAGUCACUACUCAUCAUUUUCUU
서열번호 35 hsa-miR-3670 가닥 1 AGAGCUCACAGCUGUCCUUCUCUA
서열번호 36 hsa-miR-3670 가닥 2 GAGAAGGACAGCUGUGAGCUCUUU
서열번호 37 hsa-miR-3943 가닥 1 UAGCCCCCAGGCUUCACUUGGCG
서열번호 38 hsa-miR-3943 가닥 2 CCAAGUGAAGCCUGGGGGCUAUU
서열번호 39 hsa-miR-4424 가닥 1 AGAGUUAACUCAAAAUGGACUA
서열번호 40 hsa-miR-4424 가닥 2 GUCCAUUUUGAGUUAACUCUUU
서열번호 41 hsa-miR-4461 가닥 1 GAUUGAGACUAGUAGGGCUAGGC
서열번호 42 hsa-miR-4461 가닥 2 CUAGCCCUACUAGUCUCAAUCUU
서열번호 43 hsa-miR-4477a 가닥 1 CUAUUAAGGACAUUUGUGAUUC
서열번호 44 hsa-miR-4477a 가닥 2 AUCACAAAUGUCCUUAAUAGUU
서열번호 45 hsa-miR-4477b 가닥 1 AUUAAGGACAUUUGUGAUUGAU
서열번호 46 hsa-miR-4477b 가닥 2 CAAUCACAAAUGUCCUUAAUUU
서열번호 47 hsa-miR-4765 가닥 1 UGAGUGAUUGAUAGCUAUGUUC
서열번호 48 hsa-miR-4765 가닥 2 ACAUAGCUAUCAAUCACUCAUU
서열번호 49 hsa-miR-4773 가닥 1 CAGAACAGGAGCAUAGAAAGGC
서열번호 50 hsa-miR-4773 가닥 2 CUUUCUAUGCUCCUGUUCUGUU
서열번호 51 hsa-miR-4776 가닥 1 GUGGACCAGGAUGGCAAGGGCU
서열번호 52 hsa-miR-4776 가닥 2 CUUGCCAUCCUGGUCCACUGCAU
서열번호 53 hsa-miR-4999 가닥 1 UGCUGUAUUGUCAGGUAGUGA
서열번호 54 hsa-miR-4999 가닥 2 UCACUACCUGACAAUACAGU
서열번호 55 hsa-miR-5096 가닥 1 GUUUCACCAUGUUGGUCAGGC
서열번호 56 hsa-miR-5096 가닥 2 CUGACCAACAUGGUGAAACUU
서열번호 57 hsa-miR-5697 가닥 1 UCAAGUAGUUUCAUGAUAAAGG
서열번호 58 hsa-miR-5697 가닥 2 UUUAUCAUGAAACUACUUGAUU
서열번호 59 hsa-miR-5705 가닥 1 UGUUUCGGGGCUCAUGGCCUGUG
서열번호 60 hsa-miR-5705 가닥 2 CAGGCCAUGAGCCCCGAAACAUU
서열번호 61 hsa-miR-5707 가닥 1 ACGUUUGAAUGCUGUACAAGGC
서열번호 62 hsa-miR-5707 가닥 2 CUUGUACAGCAUUCAAACGUUU
서열번호 63 hsa-miR-8053 가닥 1 UGGCGAUUUUGGAACUCAAUGGCA
서열번호 64 hsa-miR-8053 가닥 2 CCAUUGAGUUCCAAAAUCGCCAUU
서열번호 65 hsa-miR-8078 가닥 1 GGUCUAGGCCCGGUGAGAGACUC
서열번호 66 hsa-miR-8078 가닥 2 GUCUCUCACCGGGCCUAGACCUU
실시예 4: 폐암 세포주의 증식 억제 효능의 miRNA 발굴을 위한 2차 스크리닝
1차 스크리닝에서 얻어진 50 여개의 miRNA 후보군을 사용하여 측정 정밀도를 향상시켜 2차 스크리닝을 진행하였다. 실험 조건은 1차 스크리닝 조건과 동일하게 진행하였으며, 다른 점은 세포의 증식 능력을 측정하기 위한 시약으로 레사주린 대신 WST-1 시약(Roche)을 이용하였다. WST-1 이 레사주린에 비하여 신호의 세기가 보다 정량적으로 측정될 수 있는 장점이 있어 사용하였다. 각 miRNA에 의한 세포 억제 능력의 측정값을 대조군 대비 상대적인 값으로 도 3에 개시 하였으며, 양성 대조군으로서 miR-34a 또한 포함하였다.
실시예 5: 세포 자살 유도 능력 분석
스크리닝에서 사용된 방법은 정량적 의미에서 세포의 개수를 측정함으로써 상대적인 세포 증식의 억제 정도를 측정하는 방법이다. 세포의 증식을 억제하는 기전은 세포의 분열 주기 속도를 감속시키는 방법과 세포의 자살을 유도하는 방법이 있다. 본 발명에서 발견한 miRNA 의 세포 증식 억제력의 작용 기전을 분석하기 위하여 세포 자살 정도를 유세포분석기 (Fluorescence Activated Cell Sorter, FACS) 를 사용하여 분석하였다. 이를 위하여 세포를 6-well plate 에 분주하고 RNAiMAX 시약으로 해당 miRNA 를 세포에 주입한 후 48 시간 동안 상기 기술한 조건에서 세포를 배양하였다. 이 후 세포를 FIT-C 형광 염료가 표지된 아넥신V (annexin V) 로 처리한 후 유세포분석기로 분석하였다 (도 4). 분석 결과 miR-3670, miR-4477a, miR-8078 으로 처리된 대부분의 세포가 사멸된 것을 확인할 수 있다. 이는 스크리닝에서 확인된 miRNA 의 종양 성장 억제 효과가 세포의 사멸을 유발함으로써 이루어진 것임을 알 수 있다(표 3).
최종 선별 miRNA 서열
서열번호 35 hsa-miR-3670 가닥 1 AGAGCUCACAGCUGUCCUUCUCUA
서열번호 36 hsa-miR-3670 가닥 2 GAGAAGGACAGCUGUGAGCUCUUU
서열번호 67 miR-3670-IC IC GACUGGUAUAGCUGCUUUUGGAGCCUCA
서열번호 43 hsa-miR-4477a 가닥 1 CUAUUAAGGACAUUUGUGAUUC
서열번호 44 hsa-miR-4477a 가닥 2 AUCACAAAUGUCCUUAAUAGUU
서열번호 68 miR-4477a-IC IC AUCACAAAUGUCCUUAAUGGCA
서열번호 65 hsa-miR-8078 가닥 1 GGUCUAGGCCCGGUGAGAGACUC
서열번호 66 hsa-miR-8078 가닥 2 GUCUCUCACCGGGCCUAGACCUU
서열번호 69 miR-8078-IC IC CUCCACCGGGCUGACCGGCCUG
실시예 6: miRNA 에 의한 소프트 아가 (soft agar) 에서의 종양 성장 억제
소프트 아가를 이용하여 종양 세포를 배양함으로써 종양 세포로서의 특질을 측정할 수 있다. 정상 세포의 경우 성장하기 위하여 배양접시와 같은 지지대가 필요한 반면 종양 세포는 소프트 아가와 같이 물리적으로 견고한 지지대가 없는 환경에서도 성장하는 특징을 가지고 있다. 이러한 종양 특이적 성질을 사용하여 소프트 아가에서의 세포 군집 능력을 파악하였다. NCI-H460 폐암 세포주를 control miRNA, miR-34a, miR-8078, miR-3670, miR-4477a, miR-4765 로 각각 처리하여 24 시간 배양한 후, 이를 소프트 아가와 혼합하여 6 well-plate 에서 2주간 배양하였다. 세포를 크리스탈 비올렛 (crystal violet) 염료로 염색하여 각 군집의 개수를 측정하였다 (도5). 그 결과, miR-8078 및 miR-3670 으로 처리한 세포는 거의 군집을 형성하지 못하였고, miR-4477a 로 처리한 세포군의 경우는 대조군 대비 대략 30% 정도의 군집 형성 능력을 보이는 것을 확인할 수 있었다.
실시예 7: miRNA 의 타겟 mRNA 의 세포 증식 억제 효과 측정
miRNA 에 의하여 단백질 발현이 제어되는 타겟 mRNA 는 miRNA 의 서열과 부분적으로 상보적인 서열을 갖는다. miRNA 는 mRNA 의 발현을 억제하기 위하여 특히 씨앗 지역 (seed region) 의 서열이 중요한데, 이는 씨앗 지역 서열과 상보적인 서열을 갖는 mRNA 와 결합하여 유전자의 발현을 저해하기 때문이다. 그러나 씨앗 지역 서열이 8-9개의 염기로 비교적 짧기 때문에 miRNA 의 타겟이 되는 mRNA 는 소프트웨어를 사용하여 예측하게 된다. 그러나, 소프트웨어를 사용하는 경우에도 예측된 타겟 중 일부만이 실질적 타겟인 것으로 알려져 있다. 이러한 난점을 해결하기 위하여 소프트웨어를 통하여 예측된 타겟 유전자에 대하여 siRNA 를 사용하여 세포내의 함량을 저하시킨 후, 세포의 성장이 억제되는지 여부를 판단함으로써 타겟 유전자를 선정하였다. miRNA 의 타겟 mRNA 를 예측하기 위하여 이 분야에서 범용적으로 사용되는 타겟 예측 소프트웨어로 타겟스캔 (TargetScan) 을 사용하였으며, miR-3670, miR-4477a, miR-8078 의 예상 타겟으로 총 600 여종의 유전자를 선정하였다. 선정된 각 유전자에 대하여 3 종의 siRNA 를 합성하였고, 이를 사용하여 실시예 3 에서 수행한 방법과 동일하게 실험을 진행하였다. 세포를 96 well-plate 에 분주하고, 각 siRNA 로 처리한 후 48 시간 배양한 후, 레사주린 시약을 사용하여 세포 증식 능력을 측정하였다. 실시예 3 에서 처리한 방법과 동일한 방식으로 총 1800 여개 (600 여 유전자 x 3 종의 siRNA) 의 측정값 평균으로부터 각 유전자의 Z-score 를 계산하여 도 6에 개시하였다.
실시예 8: miRNA 의 타겟 mRNA 분석
miRNA 의 작용 방식은 mRNA 로부터 단백질을 생성하는 것을 저하시키며, 이와 동시에 타겟이 되는 대부분의 mRNA 의 분해를 유발시킨다. 따라서, 세포 내에 miRNA 를 주입하고 miRNA 의 타겟이 되는 mRNA 의 함량을 qPCR 을 사용하여 분석, 함량 저하를 측정함으로써 miRNA 의 타겟 mRNA 여부를 판별할 수 있는 하나의 기준으로 사용할 수 있다. 실시예 7 에서 확인된 miRNA 의 타겟 유전자를 대상으로 하여 miRNA 를 세포내로 전달한 경우 실질적으로 타겟 mRNA 가 저하되는지 여부를 측정하기 위하여, miR-3670, miR-4477a, miR-8078 을 폐암 세포주에 각각 주입하여 48 시간 배양한 후 각 세포에서 RNA 를 추출하여 RNA 함량을 정량적으로 측정하였다 (도 7). 그 결과, miR-3670, miR-4477a, miR-8078 의 예상 타겟 mRNA 의 함량이 현저히 저하되는 것을 확인할 수 있었다.
실시예 9: 루시퍼아제 측정법에 의한 타겟 mRNA 의 확인
miRNA 는 타겟 mRNA 의 3' UTR (untranslated region) 에 결합함으로써 타겟 mRNA 에서의 단백질 생성을 저해하기 때문에 miRNA 와 타겟 mRNA 와의 관계를 직접적으로 측정하는 방법으로서 루시퍼아제 측정법을 통상적으로 사용한다. 타겟스캔 (TargetScan) 소프트웨어에서 miRNA 결합 서열이 포함된 3' UTR 서열을 제공하는데 이를 상기 실시예 2 에서 기술한 바와 같이 파이어플라이 루시퍼아제 (firefly luciferase) 의 3' UTR 에 유전자 클로닝 (gene cloning) 기법으로 삽입하고, 이러한 방식으로 제작된 벡터를 해당 miRNA 와 동시에 Human Embryonic Kidney (HEK) 세포에 트랜스펙션하여 벡터의 루시퍼아제 발현량을 측정하였다. 이 때 트랜스펙션 효율을 보정하기 위하여 레닐라 루시퍼아제 (renilla luciferase) 도 동시에 트랜스펙션하여 측정치를 보정하였다. miRNA, 파이어플라이 루시퍼아제, 레닐라 루시퍼아제를 동시에 주입하고 48시간 동안 배양한 후 루미노미터 (Luminometer) 로 측정하였다 (도 9). 그 결과, 각 타겟 mRNA 가 해당 miRNA 에 의하여 직접적으로 제어된다는 것을 확인할 수 있었다.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적 기술은 단지 바람직한 실시 양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.
SEQUENCE LISTING <110> BIONEER CORPORATION <120> Pharmaceutical composition for treating cancer comprising miRNA <130> P16-B042 <150> KR10-2015-0026557 <151> 2015-02-25 <160> 69 <170> PatentIn version 3.5 <210> 1 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 1 aucacauugc cagugauuac cc 22 <210> 2 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 2 guaaucacug gcaaugugau uu 22 <210> 3 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 3 agauguccag ccacaauucu cg 22 <210> 4 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 4 agaauugcgu uuggacaauc agu 23 <210> 5 <211> 25 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 5 acuggacuug gagucagaag agugg 25 <210> 6 <211> 25 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 6 acucuucuga cuccaagucc aguuu 25 <210> 7 <211> 25 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 7 aaaaaccaca auuacuuuug cacca 25 <210> 8 <211> 25 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 8 gugcaaaagu aauugugguu uuuuu 25 <210> 9 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 9 caaagacugc aauuacuuuu gcg 23 <210> 10 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 10 caaaaguaau ugcagucuuu guu 23 <210> 11 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 11 ugaguuggcc aucugaguga g 21 <210> 12 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 12 cacucagaug gccaacucau u 21 <210> 13 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 13 aaagacauag gauagaguca ccuc 24 <210> 14 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 14 ggugacucua uccuaugucu uuuu 24 <210> 15 <211> 26 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 15 aaguaguugg uuuguaugag augguu 26 <210> 16 <211> 26 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 16 ccaucucaua caaaccaacu acuuuu 26 <210> 17 <211> 27 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 17 accuucuugu auaagcacug ugcuaaa 27 <210> 18 <211> 27 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 18 uagcacagug cuuauacaag aagguuu 27 <210> 19 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 19 caucugggca acugacugaa c 21 <210> 20 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 20 uucauucggc uguccagaug ua 22 <210> 21 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 21 uaggaugggg gugagaggug 20 <210> 22 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 22 ccucucaccc ccauccuauu 20 <210> 23 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 23 uggcuuuuaa cuuugauggc 20 <210> 24 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 24 caucaaaguu aaaagccauu 20 <210> 25 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 25 ugugacuuua agggaaaugg cg 22 <210> 26 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 26 ccauuucccu uaaagucaca uu 22 <210> 27 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 27 agaggcuuug ugcggauacg ggg 23 <210> 28 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 28 ccguauccgc acaaagccuc uuu 23 <210> 29 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 29 caaagugaug aguaauacug gcug 24 <210> 30 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 30 gccaguauua cucaucacuu uguu 24 <210> 31 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 31 aggaggcauc uugagaaaug ga 22 <210> 32 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 32 cauuucucaa gaugccuccu uu 22 <210> 33 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 33 gaaaaugaug aguagugacu gaug 24 <210> 34 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 34 ucagucacua cucaucauuu ucuu 24 <210> 35 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 35 agagcucaca gcuguccuuc ucua 24 <210> 36 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 36 gagaaggaca gcugugagcu cuuu 24 <210> 37 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 37 uagcccccag gcuucacuug gcg 23 <210> 38 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 38 ccaagugaag ccugggggcu auu 23 <210> 39 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 39 agaguuaacu caaaauggac ua 22 <210> 40 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 40 guccauuuug aguuaacucu uu 22 <210> 41 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 41 gauugagacu aguagggcua ggc 23 <210> 42 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 42 cuagcccuac uagucucaau cuu 23 <210> 43 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 43 cuauuaagga cauuugugau uc 22 <210> 44 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 44 aucacaaaug uccuuaauag uu 22 <210> 45 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 45 auuaaggaca uuugugauug au 22 <210> 46 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 46 caaucacaaa uguccuuaau uu 22 <210> 47 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 47 ugagugauug auagcuaugu uc 22 <210> 48 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 48 acauagcuau caaucacuca uu 22 <210> 49 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 49 cagaacagga gcauagaaag gc 22 <210> 50 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 50 cuuucuaugc uccuguucug uu 22 <210> 51 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 51 guggaccagg auggcaaggg cu 22 <210> 52 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 52 cuugccaucc ugguccacug cau 23 <210> 53 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 53 ugcuguauug ucagguagug a 21 <210> 54 <211> 20 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 54 ucacuaccug acaauacagu 20 <210> 55 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 55 guuucaccau guuggucagg c 21 <210> 56 <211> 21 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 56 cugaccaaca uggugaaacu u 21 <210> 57 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 57 ucaaguaguu ucaugauaaa gg 22 <210> 58 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 58 uuuaucauga aacuacuuga uu 22 <210> 59 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 59 uguuucgggg cucauggccu gug 23 <210> 60 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 60 caggccauga gccccgaaac auu 23 <210> 61 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 61 acguuugaau gcuguacaag gc 22 <210> 62 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 62 cuuguacagc auucaaacgu uu 22 <210> 63 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 63 uggcgauuuu ggaacucaau ggca 24 <210> 64 <211> 24 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 64 ccauugaguu ccaaaaucgc cauu 24 <210> 65 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 65 ggucuaggcc cggugagaga cuc 23 <210> 66 <211> 23 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 66 gucucucacc gggccuagac cuu 23 <210> 67 <211> 28 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 67 gacugguaua gcugcuuuug gagccuca 28 <210> 68 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 68 aucacaaaug uccuuaaugg ca 22 <210> 69 <211> 22 <212> RNA <213> Artificial Sequence <220> <223> Artificial sequence <400> 69 cuccaccggg cugaccggcc ug 22

Claims (10)

  1. miR-3670을 유효 성분으로 포함하는 암 치료용 약학 조성물.
  2. 제 1항에 있어서, 상기 miR-3670 는 서열 번호 35와 서열 번호 36 또는 서열 번호 67의 염기 서열로 이루어진 이중 가닥 RNA로 구성되는 이중 가닥이 유효 성분으로 포함되는 것을 특징으로 하는 약학 조성물.
  3. 삭제
  4. 삭제
  5. 제1항에 있어서, 상기 miR-3670는 암 세포의 자살 기전을 유도하여 암을 치료하는 것을 특징으로 하는 약학 조성물.
  6. 제1항에 있어서, 상기 암은 폐암, 간암, 위암, 대장암, 췌장암, 담낭 및 담도암, 유방암, 백혈병, 식도암, 비호치킨 림프종, 갑상선암, 자궁경부암, 피부암의 원발성 암과 이로부터 기타 장기로 전이되어 유발되는 전이암 및 비정상적인 과다 세포 분열을 촉진하여 생성되는 종양성 세포 질환으로 구성되는 군으로부터 선택된 1종 이상의 암인 것을 특징으로 하는 약학 조성물.
  7. 제1항, 제2항 및 제5항 중 어느 한 항에 있어서, 상기 miR-3670는 miR-3670유도체인 것을 특징으로 하는 조성물.
  8. 제7항에 있어서, 상기 miRNA 유도체는 RNA 인산 뼈대 구조 (phosphate backbone structure)를 황 등의 다른 원소로 치환한 형태인 포스포로사이오에이트 (phosphorothiolate) 구조를 부분적으로 포함하는 형태; RNA 대신 DNA, PNA(petide nucleic acids) 및 LNA(locked nucleic acid) 분자로의 전체 또는 부분적으로 치환된 형태; 및 RNA 당의 2'수산화기를 메틸화, 메톡시화, 플르오르화 등의 기능성 구조로 치환한 형태로 구성된 군에서 선택되는 것을 특징으로 하는 조성물.
  9. 제7항에 있어서, 상기 miRNA 유도체는 pri-miRNA 또는 precursor miRNA의 miRNA 전구체 형태; 또는 플라스미드 형태의 miRNA 전구체로 구성되는 것을 특징으로 하는 조성물.
  10. 제9항에 있어서, 상기 miRNA 전구체는 RNA 인산 뼈대 구조 (phosphate backbone structure)를 황 등의 다른 원소로 치환한 형태인 포스포로사이오에이트 (phosphorothiolate) 구조를 부분적으로 포함하는 형태; RNA 대신 DNA, PNA(petide nucleic acids) 및 LNA(locked nucleic acid) 분자로의 전체 또는 부분적으로 치환된 형태; 및 RNA 당의 2'수산화기를 메틸화, 메톡시화, 플르오르화 등의 기능성 구조로 치환한 형태로 구성된 군에서 선택되는 것을 특징으로 하는 조성물.
KR1020160022462A 2015-02-25 2016-02-25 마이크로 rna 를 유효 성분으로 포함하는 암 치료용 약학 조성물 KR101862080B1 (ko)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020150026557 2015-02-25
KR20150026557 2015-02-25

Related Child Applications (1)

Application Number Title Priority Date Filing Date
KR1020180055329A Division KR101960067B1 (ko) 2015-02-25 2018-05-15 마이크로 rna를 유효 성분으로 포함하는 암 치료용 약학 조성물

Publications (2)

Publication Number Publication Date
KR20160103949A KR20160103949A (ko) 2016-09-02
KR101862080B1 true KR101862080B1 (ko) 2018-07-04

Family

ID=56789628

Family Applications (2)

Application Number Title Priority Date Filing Date
KR1020160022462A KR101862080B1 (ko) 2015-02-25 2016-02-25 마이크로 rna 를 유효 성분으로 포함하는 암 치료용 약학 조성물
KR1020180055329A KR101960067B1 (ko) 2015-02-25 2018-05-15 마이크로 rna를 유효 성분으로 포함하는 암 치료용 약학 조성물

Family Applications After (1)

Application Number Title Priority Date Filing Date
KR1020180055329A KR101960067B1 (ko) 2015-02-25 2018-05-15 마이크로 rna를 유효 성분으로 포함하는 암 치료용 약학 조성물

Country Status (10)

Country Link
US (2) US10351849B2 (ko)
EP (1) EP3263135B1 (ko)
JP (1) JP6538183B2 (ko)
KR (2) KR101862080B1 (ko)
CN (2) CN113633656A (ko)
AU (1) AU2016224201B2 (ko)
BR (1) BR112017018318A2 (ko)
CA (2) CA2977624C (ko)
RU (1) RU2686313C2 (ko)
WO (1) WO2016137235A2 (ko)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2017100253A (ru) 2014-06-12 2018-07-17 Торэй Индастриз, Инк. Набор или устройство для обнаружения рака предстательной железы и способ обнаружения
KR101861738B1 (ko) * 2016-08-24 2018-05-29 (주)바이오니아 마이크로 rna를 포함하는 이중나선 올리고 rna 구조체
CN107058474B (zh) * 2016-11-03 2020-09-01 中国人民解放军陆军军医大学 一种通过血浆microRNA-3591-3p诊断急性高山病的诊断试剂盒
KR20180075139A (ko) * 2016-12-26 2018-07-04 한국원자력의학원 Ccnd3 또는 pak2 유전자의 발현을 저해하는 암을 치료하기 위한 약학적 조성물
KR102110103B1 (ko) * 2017-06-16 2020-05-13 (주)프로스테믹스 암의 예방 또는 치료용 약학적 조성물
WO2019093308A1 (ja) * 2017-11-09 2019-05-16 国立大学法人広島大学 ｍｉＲＮＡを含むがん治療用医薬組成物
WO2019103581A1 (ko) * 2017-11-27 2019-05-31 (주)프로스테믹스 이중 가닥의 올리고뉴클레오티드 및 그 제조 방법
WO2019103572A1 (ko) * 2017-11-27 2019-05-31 (주)프로스테믹스 Mirna를 포함하는 탈모 방지 또는 발모 촉진용 조성물
KR102189991B1 (ko) * 2017-11-27 2020-12-11 (주)프로스테믹스 miRNA를 포함하는 상처 치료 또는 피부 개선용 조성물
WO2019103578A1 (ko) * 2017-11-27 2019-05-31 (주)프로스테믹스 올리고뉴클레오티드 및 이를 포함하는 암의 예방 또는 치료용 약학적 조성물
CN107881237B (zh) * 2017-12-01 2020-11-20 唐山市人民医院 肺癌诊断标记物microRNA-4317及在药物和诊断试剂盒中的应用
KR102141124B1 (ko) * 2018-01-30 2020-08-04 (주)바이오니아 이중 가닥 miRNA를 포함하는 이중나선 올리고뉴클레오타이드 구조체 및 이의 용도
US10987428B2 (en) * 2018-06-01 2021-04-27 City Of Hope Phosphorothioate-conjugated miRNAs and methods of using the same
JP7378739B2 (ja) 2018-08-10 2023-11-14 東レ株式会社 前立腺がんの検出のためのキット、デバイス及び方法
KR102178919B1 (ko) * 2018-11-26 2020-11-13 순천향대학교 산학협력단 당뇨병성 신증 진단을 위한 마이크로rna 바이오마커 및 이의 용도
KR102133205B1 (ko) 2018-12-05 2020-07-13 충북대학교 산학협력단 PNA-pHLIP 접합체를 유효성분으로 포함하는 암 예방 또는 치료용 약학적 조성물
KR102418779B1 (ko) * 2018-12-12 2022-07-08 (주)프로스테믹스 신규한 miRNA 유사체 및 이의 용도
WO2020235671A1 (ja) * 2019-05-23 2020-11-26 国立大学法人大阪大学 性ホルモン非感受性ｇｒｅｂ１陽性腫瘍の治療剤
CN110184338B (zh) * 2019-05-31 2023-04-07 南方医科大学第三附属医院（广东省骨科研究院） 脑脊液外泌体miRNA在MMD诊断和治疗中的应用
JP7545678B2 (ja) 2019-06-05 2024-09-05 株式会社キャンサーステムテック 癌治療剤
KR102085260B1 (ko) 2019-06-19 2020-03-05 한국원자력의학원 Ccnd3 또는 pak2 유전자의 발현을 저해하는 암을 치료하기 위한 약학적 조성물
CN110607368B (zh) * 2019-09-19 2021-07-13 西安交通大学 miRNA3926-1基因作为胰腺癌诊断和疗效标志物的应用
CN111467504A (zh) * 2020-03-13 2020-07-31 南方医科大学 miR-4469在制备抗结直肠癌药物中的应用
CN111349704B (zh) * 2020-03-17 2020-11-24 河北医科大学第三医院 肝癌的诊断产品和治疗组合物
CN111387143A (zh) * 2020-04-02 2020-07-10 华北理工大学 miRNA-203a-3p在开发抑制胰腺癌药物中的应用
CN111466339A (zh) * 2020-04-02 2020-07-31 华北理工大学 miRNA-203a-3p在促进胰腺癌细胞增殖和迁移中的应用
WO2021240533A1 (en) * 2020-05-29 2021-12-02 National Institute Of Immunology Dna damage dependent microrna signature for cancers, methods and uses related thereto
CN114058697B (zh) * 2020-07-29 2023-08-18 四川大学华西医院 检测外泌体miR-6774-3p或miR-6776-5p的试剂的用途
CN114058698B (zh) * 2020-07-29 2023-08-15 四川大学华西医院 检测外泌体miR-6879-5p的试剂在制备甲状腺癌转移检测试剂盒中的用途
US20220119812A1 (en) * 2020-10-20 2022-04-21 Duquesne University Of The Holy Spirit Micro rna interactions as therapeutic targets for covid-19 and other viral infections
CN112094913B (zh) * 2020-11-10 2021-03-30 广州市锐博生物科技有限公司 结直肠癌生物标志物及其用途
AU2022226837A1 (en) * 2021-02-25 2023-07-20 Bioneer Corporation Composition for alleviating hair graying, promoting hair growth and/or preventing or alleviating hair loss, comprising double-stranded mirna as active ingredient
CN113041255B (zh) * 2021-04-13 2022-10-11 上海中医药大学 一种新发现miRNA–mRNA调控轴介导肺腺癌NCI-H1299细胞焦亡的方法
CN113981074A (zh) * 2021-12-10 2022-01-28 石河子大学 一种与2型糖尿病相关的microRNA及其应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140080894A1 (en) 2011-03-02 2014-03-20 David L. McElligott Enhanced biodistribution of oligomers
WO2014048441A1 (en) 2012-09-26 2014-04-03 Mirrx Therapeutics Oligomers with improved off-target profile
WO2014100252A1 (en) 2012-12-18 2014-06-26 University Of Washington Through Its Center For Commercialization Methods and compositions to modulate rna processing

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US15071A (en) * 1856-06-10 John h
CA2604288C (en) * 2005-04-12 2021-07-06 Universite Libre De Bruxelles Use of a galectin-1-targeted rnai-based approach for the treatment of cancer
US20090227533A1 (en) 2007-06-08 2009-09-10 Bader Andreas G miR-34 Regulated Genes and Pathways as Targets for Therapeutic Intervention
KR101325186B1 (ko) * 2008-01-23 2013-11-07 (주)바이오니아 이중가닥 ｍｉＲＮＡ를 유효성분으로 포함하는 항암제
WO2009128805A1 (en) 2008-04-17 2009-10-22 The Johns Hopkins University On01910. na enhances chemotherapeutic agent activity in drug-resistant tumors
US20120302626A1 (en) 2009-12-04 2012-11-29 Sandeep Dave Microrna and use thereof in identification of b cell malignancies
CN103505743A (zh) * 2012-06-21 2014-01-15 北京命码生科科技有限公司 含功能性microRNA/siRNA的细胞微粒子及其应用
EP2919817A4 (en) * 2012-11-16 2016-10-19 Univ Texas MIARN AS NEW THERAPEUTIC ADJUVANTS AND BIOMARKERS OF THE PROGNOSIS AND TREATMENT OF CHEMORESISTING BREAST CANCER
CN112094913B (zh) * 2020-11-10 2021-03-30 广州市锐博生物科技有限公司 结直肠癌生物标志物及其用途

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140080894A1 (en) 2011-03-02 2014-03-20 David L. McElligott Enhanced biodistribution of oligomers
WO2014048441A1 (en) 2012-09-26 2014-04-03 Mirrx Therapeutics Oligomers with improved off-target profile
WO2014100252A1 (en) 2012-12-18 2014-06-26 University Of Washington Through Its Center For Commercialization Methods and compositions to modulate rna processing

Also Published As

Publication number Publication date
CN113633656A (zh) 2021-11-12
JP2018507866A (ja) 2018-03-22
CN107454843A (zh) 2017-12-08
AU2016224201B2 (en) 2018-07-05
EP3263135A4 (en) 2018-09-19
KR20160103949A (ko) 2016-09-02
US20190218555A1 (en) 2019-07-18
CA2977624A1 (en) 2016-09-01
US20180030440A1 (en) 2018-02-01
EP3263135A2 (en) 2018-01-03
US10612026B2 (en) 2020-04-07
KR20180054549A (ko) 2018-05-24
WO2016137235A2 (ko) 2016-09-01
AU2016224201A1 (en) 2017-09-21
JP6538183B2 (ja) 2019-07-03
BR112017018318A2 (ko) 2018-07-10
CA2977624C (en) 2021-11-30
RU2017132895A3 (ko) 2019-03-25
CA3134991A1 (en) 2016-09-01
RU2017132895A (ru) 2019-03-25
RU2686313C2 (ru) 2019-04-25
KR101960067B1 (ko) 2019-03-20
EP3263135B1 (en) 2020-01-15
CN107454843B (zh) 2021-07-30
US10351849B2 (en) 2019-07-16
WO2016137235A3 (ko) 2016-10-20
WO2016137235A9 (ko) 2016-11-24

Similar Documents

Publication Publication Date Title
KR101960067B1 (ko) 마이크로 rna를 유효 성분으로 포함하는 암 치료용 약학 조성물
CA2681568C (en) Oligonucleotides for modulating target rna activity
EP2550360B1 (en) Bivalent antisense oligonucleotides
US9284554B2 (en) Micro-RNA scaffolds and non-naturally occurring micro-RNAs
US20180201928A1 (en) Micromirs
EP2208499A1 (en) Nucleic acid capable of regulating the proliferation of cell
US20130065778A1 (en) MicroRNA Signatures Predicting Responsiveness To Anti-HER2 Therapy
US20120219958A1 (en) MicroRNA Signatures Differentiating Uterine and Ovarian Papillary Serous Tumors
EP2298359A1 (en) Nucleic acid capable of controlling degranulation of mast cell
CN101641440A (zh) 用于调节靶rna活性的寡核苷酸
AU2014250708B2 (en) Oligonucleotides for modulating target RNA activity

Legal Events

Date Code Title Description
A201 Request for examination
E902 Notification of reason for refusal
E701 Decision to grant or registration of patent right
A107 Divisional application of patent
GRNT Written decision to grant