CN116327796B - YTHDF1调控LINC00900 m6A甲基化对胶质瘤干细胞生长和自我更新的影响 - Google Patents
YTHDF1调控LINC00900 m6A甲基化对胶质瘤干细胞生长和自我更新的影响 Download PDFInfo
- Publication number
- CN116327796B CN116327796B CN202310277195.3A CN202310277195A CN116327796B CN 116327796 B CN116327796 B CN 116327796B CN 202310277195 A CN202310277195 A CN 202310277195A CN 116327796 B CN116327796 B CN 116327796B
- Authority
- CN
- China
- Prior art keywords
- linc00900
- ythdf1
- expression
- self
- renewal
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 230000011987 methylation Effects 0.000 title claims abstract description 16
- 238000007069 methylation reaction Methods 0.000 title claims abstract description 16
- 206010018338 Glioma Diseases 0.000 title abstract description 39
- 208000032612 Glial tumor Diseases 0.000 title abstract description 35
- 230000000694 effects Effects 0.000 title abstract description 26
- 210000000130 stem cell Anatomy 0.000 title abstract description 8
- 230000010261 cell growth Effects 0.000 title abstract description 4
- 101000744742 Homo sapiens YTH domain-containing family protein 1 Proteins 0.000 claims abstract description 79
- 102100039647 YTH domain-containing family protein 1 Human genes 0.000 claims abstract description 79
- 230000014509 gene expression Effects 0.000 claims abstract description 53
- 230000001105 regulatory effect Effects 0.000 claims abstract description 11
- 239000000556 agonist Substances 0.000 claims description 7
- 239000002773 nucleotide Substances 0.000 claims description 7
- 125000003729 nucleotide group Chemical group 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000001737 promoting effect Effects 0.000 claims description 3
- 230000003827 upregulation Effects 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 238000000423 cell based assay Methods 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract description 40
- 230000035755 proliferation Effects 0.000 abstract description 25
- 230000009545 invasion Effects 0.000 abstract description 23
- 238000001514 detection method Methods 0.000 abstract description 21
- 238000011529 RT qPCR Methods 0.000 abstract description 19
- 108091048739 miR-1205 stem-loop Proteins 0.000 abstract description 18
- 238000001262 western blot Methods 0.000 abstract description 13
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 abstract description 12
- 108060001084 Luciferase Proteins 0.000 abstract description 10
- 239000005089 Luciferase Substances 0.000 abstract description 10
- 108010087230 Sincalide Proteins 0.000 abstract description 9
- 238000010609 cell counting kit-8 assay Methods 0.000 abstract description 9
- 108020004459 Small interfering RNA Proteins 0.000 abstract description 7
- 238000012360 testing method Methods 0.000 abstract description 7
- 238000011160 research Methods 0.000 abstract description 6
- 230000001276 controlling effect Effects 0.000 abstract description 4
- 230000033228 biological regulation Effects 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 238000003364 immunohistochemistry Methods 0.000 abstract 1
- 230000002018 overexpression Effects 0.000 description 21
- 238000002474 experimental method Methods 0.000 description 19
- 206010028980 Neoplasm Diseases 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 13
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 12
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 241000713666 Lentivirus Species 0.000 description 9
- 108091046869 Telomeric non-coding RNA Proteins 0.000 description 9
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 6
- 241000700605 Viruses Species 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 108010092160 Dactinomycin Proteins 0.000 description 4
- 101000959153 Homo sapiens RNA demethylase ALKBH5 Proteins 0.000 description 4
- 102100039083 RNA demethylase ALKBH5 Human genes 0.000 description 4
- 108091027967 Small hairpin RNA Proteins 0.000 description 4
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 229960000640 dactinomycin Drugs 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000002452 interceptive effect Effects 0.000 description 4
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 3
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 3
- 101100447432 Danio rerio gapdh-2 gene Proteins 0.000 description 3
- 101100214180 Drosophila melanogaster Ythdf gene Proteins 0.000 description 3
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- 101150112014 Gapdh gene Proteins 0.000 description 3
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 3
- 101000967135 Homo sapiens N6-adenosine-methyltransferase catalytic subunit Proteins 0.000 description 3
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 3
- 102100040619 N6-adenosine-methyltransferase catalytic subunit Human genes 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000002055 immunohistochemical effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 108010008599 Forkhead Box Protein M1 Proteins 0.000 description 2
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 2
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 2
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000001973 epigenetic effect Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000013115 immunohistochemical detection Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000009456 molecular mechanism Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- CKOMXBHMKXXTNW-UHFFFAOYSA-N 6-methyladenine Chemical compound CNC1=NC=NC2=C1N=CN2 CKOMXBHMKXXTNW-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 244000050510 Cunninghamia lanceolata Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101001013582 Homo sapiens N6-adenosine-methyltransferase non-catalytic subunit Proteins 0.000 description 1
- 101000572986 Homo sapiens POU domain, class 3, transcription factor 2 Proteins 0.000 description 1
- 101000740204 Homo sapiens Sal-like protein 2 Proteins 0.000 description 1
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 1
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 102000016397 Methyltransferase Human genes 0.000 description 1
- 102100031578 N6-adenosine-methyltransferase non-catalytic subunit Human genes 0.000 description 1
- 102000005803 Oligodendrocyte Transcription Factor 2 Human genes 0.000 description 1
- 108010019644 Oligodendrocyte Transcription Factor 2 Proteins 0.000 description 1
- 102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 230000006093 RNA methylation Effects 0.000 description 1
- 102100037205 Sal-like protein 2 Human genes 0.000 description 1
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 1
- 108091007416 X-inactive specific transcript Proteins 0.000 description 1
- 108091035715 XIST (gene) Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 101150077246 gas5 gene Proteins 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 230000008266 oncogenic mechanism Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000011127 radiochemotherapy Methods 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4705—Regulators; Modulating activity stimulating, promoting or activating activity
-
- 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
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0618—Cells of the nervous system
- C12N5/0622—Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0693—Tumour cells; Cancer cells
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了YTHDF1调控LINC00900m6A甲基化对胶质瘤干细胞生长和自我更新的影响，属于生物医药领域。本发明通过qRT‑PCR、westernblot、免疫组化、CCK‑8检测、Transwell检测、成球试验、siRNA技术、荧光素酶活性实验、RNApull‑dwon和RIP实验探究了胶质瘤组织中YTHDF1和LINC00900的关系，发现YTHDF1通过调控LINC00900稳定性，促进LINC00900的表达，进而影响胶质瘤细胞的增殖、侵袭和自我更新，并进一步探究了LINC00900通过调控miR‑1205/STAT3信号轴影响胶质瘤细胞的增殖、侵袭和自我更新。
Description
技术领域
本发明涉及YTHDF1调控LINC00900 m6A甲基化对胶质瘤干细胞生长和自我更新的影响，属于生物医药领域。
背景技术
胶质瘤是最常见的脑肿瘤之一。尽管采用了手术切除、放化疗等治疗手段，但是患者预后较差，主要原因是肿瘤复发和放化疗的耐药性。研究表明，胶质瘤的复发和耐药性与胶质瘤干细胞(glioma stem-like cells,GSCs)密切相关。因此，以GSC为研究对象，研究其在胶质瘤中的特点及功能，可以更深入的揭示胶质瘤的发生、发展以及复发的原因，为胶质瘤的治疗提供新的思路。
表观遗传学异常被认为是最重要的致癌机制之一。RNA甲基化是表观遗传学的重要研究领域。N6-甲基腺嘌呤(N6-methyladenosine,m6A)是RNA上最丰富的内部修饰，受到甲基转移酶、去甲基化酶动态可逆的调控，并且通过与m6A读取蛋白的结合影响RNA的加工和代谢过程，调控基因表达。m6ARNA甲基化修饰的异常与胶质瘤的发生发展密切相关。Cui等研究发现干扰METTL3或METTL14显著促进了GSCs的生长、自我更新和肿瘤发生，相反干扰去甲基酶FTO则显著抑制了GSCs生长和自我更新。Visvanathan等发现METTL3在GSCs中高表达，沉默METTL3可显著抑制GSCs细胞生长以及干细胞特异性基因SSEA1、胶质瘤重编程因子POU3F2、SOX2、SALL2和OLIG2的表达。ALKBH5是一种m6A去甲基酶，研究发现ALKBH5在GSCs中高表达，干扰ALKBH5可显著抑制GSCs的增殖，机制分析发现ALKBH5调控FOXM1转录本的去甲基化，导致FOXM1表达增强；还可通过下调DNA损伤应答基因CHK1等的表达，显著促进GSCs的放疗敏感性。以上研究表明，m6A甲基化在调控GSCs自我更新和放化疗敏感性中发挥重要作用。YTHDF1是介导m6A修饰的m6A结合蛋白，研究报道YTHDF1在胶质瘤组织中显著高表达，敲低YTHDF1可显著抑制GSCs的成球、侵袭和干细胞标志物CD133、NANOG、OCT4的表达。然而。YTHDF1调控GSCs自我更新和侵袭能力的分子机制尚不清楚。
长链非编码RNA(long non-coding RNA,lncRNA)是一类转录本长度超过200个核苷酸的RNA，无蛋白编码功能。研究表明，lncRNA可通过多种分子机制在肿瘤发生发展过程中发挥重要的调节作用。作为基因和蛋白调控的多面手，lncRNA上也有m6A修饰的形成。2012年Cell杂志的一篇文章在报道m6A检测技术获得突破的同时，还对不同RNA上的m6A修饰进行了分析，发现m6A不仅在mRNA上有分布，在lncRNA等非编码RNA上也大量存在。随后，越来越多的研究证实lncRNA上存在m6A修饰，且m6A可通过调节lncRNA的表达水平影响肿瘤的发生发展，如lncRNARP11、XIST、GAS5等。然而，目前人们对m6A调控lncRNA的机制认识还只是冰山一角，还有非常多的科学问题需要进一步的明确。
LINC00900是一个新发现的lncRNA，Wang等的研究发现LINC00900在胶质瘤中高表达，且发生了m6A甲基化修饰。我们采用m6A修饰位点预测网站SRAMP预测发现，LINC00900上存在多个m6A甲基化位点，其中预测结果显示high confidence和very high confidence的m6A结合位点就有9个，提示LINC00900受到m6A甲基化的调控。进一步采用m6A2Target数据库分析显示LINC00900可与YTHDF1直接结合，提示YTHDF1可通过调节LINC00900的m6A甲基化，影响LINC00900的表达水平。
发明内容
本发明的第一个目的是提供YTHDF1在制备LINC00900激动剂中的应用，所述YTHDF1的核苷酸序列如SEQ ID NO.1所示。
在一种实施方式中，所述激动剂用于调控LINC00900表达上调，同时促进LINC00900m6A甲基化。
本发明的第二个目的是提供LINC00900在制备miR-1205抑制剂中的应用，所述LINC00900的核苷酸序列如SEQ ID NO.2所示。
在一种实施方式中，所述抑制剂用于抑制miR-1205的表达。
本发明的第三个目的是提供LINC00900在制备STAT3激动剂中的应用，所述LINC00900的核苷酸序列如SEQ ID NO.2所示。
在一种实施方式中，所述激动剂用于上调STAT3的表达。
本发明的第四个目的是提供LINC00900在制备促进胶质瘤细胞进展的产品中的应用
在一种实施方式中，所述应用不以疾病的治疗和诊断为目的。
在一种实施方式中，所述LINC00900的核苷酸序列如SEQ ID NO.2所示。
在一种实施方式中，所述胶质瘤细胞进展包括胶质瘤细胞的增殖、侵袭和自我更新。
在一种实施方式中，所述产品包括试剂或试剂盒。
在一种实施方式中，所述试剂为固态或液态。
在一种实施方式中，所述试剂或试剂盒中，将LINC00900构建为过表达质粒或过表达慢病毒载体或敲除慢病毒载体或siRNA。
有益效果：
本发明通过qRT-PCR、western blot、免疫组化、CCK-8检测、Transwell检测、成球试验、siRNA技术、荧光素酶活性实验、RNApull-dwon和RIP实验探究了胶质瘤组织中YTHDF1和LINC00900的关系，发现YTHDF1通过调控LINC00900稳定性，促进LINC00900的表达，进而影响胶质瘤细胞的增殖、侵袭和自我更新，并进一步探究了LINC00900通过调控miR-1205/STAT3信号轴影响胶质瘤细胞的增殖、侵袭和自我更新。
附图说明
图1临床水平检测胶质瘤组织中YTHDF1和LINC00900的表达水平；A，qRT-PCR和检测YTHDF1和LINC00900的表达水平，B，western blot检测YTHDF1和LINC00900的表达水平，C，免疫组化检测YTHDF1的表达水平，D，MeRIP-PCR检测LINC00900的m6A甲基化水平。
图2体外研究YTHDF1对GSCs增殖、侵袭和自我更新的作用；A，qRT-PCR和westernblot检测4种细胞中YTHDF1的表达水平，B，干扰YTHDF1的表达水平，C，CCK-8检测过表达或干扰YTHDF1对GSCs增殖的影响，D，Transwell检测过表达或干扰YTHDF1对GSCs侵袭的影响，E，成球实验检测过表达或干扰YTHDF1对GSCs自我更新能力的影响。
图3探讨YTHDF1调控LINC00900的稳定性；A，采用qRT-PCR检测LINC00900的表达水平，B，RNApulldown和RIP证明GSC-87、GSC-251细胞中YTHDF1蛋白与LINC00900的直接结合，C，放线菌素D处理过表达YTHDF1细胞。
图4探讨YTHDF1通过调控LINC00900 m6A甲基化影响GSCs增殖、侵袭和自我更新；A，CCK-8检测干扰LINC00900对GSCs增殖的影响，B，Transwell检测干扰LINC00900对GSCs侵袭的影响，C，成球实验检测干扰LINC00900对GSCs自我更新能力的影响。
图5探讨LINC00900通过调控miR-1205/STAT3信号轴影响GSCs增殖、侵袭和自我更新；A，荧光素酶报告基因实验检测miR-1205mimic和LINC00900的表达水平，B，qRT-PCR和western blot检测miR-1205mimic和LINC00900的表达水平，C，qRT-PCR检测miR-1205mimic和LINC00900的表达水平对STAT3的影响，D，western blot检测miR-1205mimic和LINC00900的表达水平对STAT3的影响，E，CCK-8检测miR-1205mimic对LINC00900的影响，F，Transwell检测miR-1205mimic对LINC00900的影响，G，成球实验检测miR-1205mimic对LINC00900的影响。
具体实施方式
以下结合说明书附图和具体实施例来进一步说明本发明，但实施例并不对本发明做任何形式的限定。除非特别说明，本发明采用的试剂、方法和设备为本技术领域常规试剂、方法和设备。
下述实施例中涉及到的qRT-PCR、western blot、免疫组化、CCK-8检测、Transwell检测、成球试验、siRNA技术、荧光素酶活性实验、RNApull-dwon和RIP实验均为常规实验操作。
实施例1临床水平检测胶质瘤组织中YTHDF1和LINC00900的表达水平
收集约20例胶质瘤患者肿瘤组织和癌旁组织。
(1)采用qRT-PCR和western blot检测YTHDF1和LINC00900的表达水平。
首先以20例胶质瘤患者肿瘤组织和癌旁组织为模板，以Gapdh为内参，利用引物YTHDF1(human)-RT-F/YTHDF1(human)-RT-R为引物，通过qRT-PCR检测YTHDF1的表达水平。结果如图1A所示，相比于癌旁组织，在RNA水平上，胶质瘤患者肿瘤组织中的YTHDF1和LINC00900的表达水平显著升高；同样的，在蛋白水平上，胶质瘤患者肿瘤组织中的YTHDF1的表达水平显著高于癌旁组织(图1B)。
LINC00900(human)-RT-F：ATGTGTTTCTTTAGGATGAGAGGTG；
LINC00900(human)-RT-R：GAGTGTCTGTATTAGTTGTATTGGG；
YTHDF1(human)-RT-F：AAGTGGAAGGGGAAGTTTGATGT；
YTHDF1(human)-RT-R：ATGGAGGTTGTGTGCTTGTAGGA；
Gapdh(human)-RT-F:GGAGCGAGATCCCTCCAAAAT；
Gapdh(human)-RT-R:GGCTGTTGTCATACTTCTCATGG；
(2)免疫组化检测YTHDF1的表达水平
选取20例胶质瘤患者肿瘤组织和癌旁组织进行常规福尔马林固定、酒精脱水、石蜡包埋，切成4μm厚的切片，随后利用YTHDF1(proteintech)和小鼠二步法检测试剂盒(中杉金桥)进行免疫组化实验。
结果如图1C显示，YTHDF1在肿瘤组织中的表达水平略高于癌旁组织中的表达水平，与qRT-PCR和western blot检测结果一致。
(3)采用MeRIP-PCR检测LINC00900的m6A甲基化水平。
使用Magna m6ARNA甲基化免疫沉淀试剂盒，按照试剂盒说明书进行免疫沉淀实验。并qRT-PCR检测富集得到的RNA。
结果如图1D显示，胶质瘤组织中的LINC00900转录本富含m6A，提示胶质瘤组织中富含m6A的LINC00900转录本可能是其异常表达的原因之一。
以上结果说明，YTHDF1和LINC00900在胶质瘤组织中显著上调，而在胶质瘤组织中，LINC00900转录本中存在较高的m6A修饰水平。
实施例2体外研究YTHDF1对GSCs增殖、侵袭和自我更新的作用
体外培养人胶质瘤细胞系(U87、U251)，分别分离胶质瘤干细胞(GSC-87、GSC-251)。用Neurobasal完全培养基(Neurobasal培养基、20ng/ml bFGF、20ng/ml EGF、1mg/ml肝素、100U/ml青霉素/链霉素)重悬人胶质瘤细胞系。将细胞密度调整到2×105/mL，加入一个新的细胞培养瓶中进行培养，每2-3天更换一次新的Neurobasal完全培养基。将胶质瘤肿瘤球直径增大至约150～200μm(约7天)后，收集胶质瘤肿瘤球，用活化酶消化液消化。收集单细胞悬液并进行传代培养。成功诱导U87和U251干细胞，得到GSC-U87和GSC-U251。
(1)采用qRT-PCR和western blot检测U87、U251、GSC-87、GSC-251中YTHDF1的表达水平。
结果如图2A显示，GSC-U87和GSC-U251细胞中YTHDF1的mRNA和蛋白水平显著高于U87和U251细胞。
(2)构建YTHDF1过表达载体(Lv-YTHDF1)及对照(Lv-NC)，合成特异性敲低YTHDF1的shRNA(Lv-shRNA-1、Lv-shRNA-2和Lv-shRNA-3)及对照shRNA(Lv-sh-NC)，并交由交由北京欧林格生物科技有限公司进行慢病毒的包装。
将YTHDF1的过表达慢病毒和干扰慢病毒分别转染GSC-87、GSC-251，得到过表达或干扰YTHDF1的细胞悬液。
结果如图2B所示，YTHDF1敲除慢病毒显著下调GSC-87和GSC-251细胞中YTHDF1的mRNA和蛋白水平，其中Lv-shRNA-2的敲除效率最好(Lv-shRNA-2的核苷酸序列为GTTCGTTACATCAGAAGGATA)；YTHDF1过表达慢病毒显著上调GSC-87和GSC-251细胞中YTHDF1的mRNA和蛋白水平。
(3)采用CCK-8检测过表达或干扰YTHDF1对GSCs增殖的影响；
将过表达YTHDF1的细胞悬液或利用Lv-shRNA-2干扰YTHDF1的细胞悬液以2000个细胞/孔的密度加入到96孔板中。24h后，每孔中加入10μL CCK-8溶液。用分光光度计测量450nm波长处的吸光度值。
CCK8实验结果如图2C显示，过表达YTHDF1显著增加了GSC-87和GSC-251细胞的增殖，而干扰YTHDF1显著降低了GSC-87和GSC-251细胞的增殖。
(4)Transwell检测过表达或干扰YTHDF1对GSCs侵袭的影响；
收集过表达或干扰YTHDF1的细胞，加入Transwell的上腔室(含基质)，在下腔室中加入含10％胎牛血清的Neurobasal培养基。将转孔细胞置于含5％二氧化碳的培养箱中，培养时间为37℃。24h后，弃置上腔室培养液，用40g/L多聚甲醛固定15分钟，PBS洗涤，结晶紫染色5分钟。用棉签轻轻擦拭腔室底膜上方的细胞。干燥后，将腔室置于光学显微镜下进行观察和计数。
Transwell实验结果如图2D显示，过表达YTHDF1显著提高了GSC-87和GSC-251细胞的侵袭能力，而干扰YTHDF1显著降低GSC-87和GSC-251细胞的侵袭能力。
(5)成球实验检测过表达或干扰YTHDF1对GSCs自我更新能力的影响。
将过表达或干扰YTHDF1的细胞接种在24孔板上，Neurobasal培养基中添加20mg/ml B27、20ng/ml EGF和20ng/ml bFGF。每周两次在Neurobasal培养基中加入EGF和bFGF。培养2～3周后，观察并计算每孔的球形成数。
肿瘤球形成实验结果如图2E显示，过表达YTHDF1显著提高了GSC-87和GSC-251细胞的肿瘤球形成能力，而干扰YTHDF1显著降低了GSC-87和GSC-251细胞的肿瘤球形成能力。
上述结果表明，过表达YTHDF1可促进GSCs的增殖、侵袭和自我更新。
实施例3探讨YTHDF1调控LINC00900的稳定性
(1)采用qRT-PCR检测LINC00900的表达水平。
结果如图3A显示，过表达YTHDF1的GSCs中LINC00900的表达水平升高，而敲除YTHDF1的GSCs中LINC00900的表达水平降低。
(2)RNApulldown和RIP证明GSC-87、GSC-251细胞中YTHDF1蛋白与LINC00900的直接结合。
RNApulldown：裂解过表达或敲除YTHDF1的GSCs细胞，离心收集上清。加入0.4μg生物素标记的RNA，然后加入0.5mLRIP缓冲液，37C孵育1h。加入50μL琼脂糖珠，室温孵育1h。用RIP缓冲液洗涤后，Western blot检测目的蛋白。
RIP：按照RIP试剂盒说明书进行。过表达或敲除YTHDF1的GSCs细胞被裂解，并与IgG或YTHDF1抗体一起孵育。提取并纯化RNA。最后，采用qRT-PCR检测目的基因的表达。
结果如图3B显示，采用RNA下拉实验和RIP实验证明了YTHDF1蛋白与LINC00900在GSCs细胞中的结合，RNA下拉结果显示，生物素标记的LINC00900(Bio-LINC00900)下拉复合物含有YTHDF1蛋白。同时，RIP实验结果进一步表明，在YTHDF1抗体下拉复合物中发现了LINC00900。
这些结果表明了LINC00900与YTHDF1之间的结合关系。
(3)采用放线菌素D(Actinomycin D)处理转染YTHDF1过表达载体及对照，或YTHDF1shRNA及对照shRNA的GSC-87、GSC-251。采用qRT-PCR检测处理不同时间(0、2、4、6h)LINC00900的表达水平，观察对LINC00900稳定性的影响。将感染了YTHDF1干扰慢病毒及对照慢病毒的GSC-87、GSC-251接种于6孔板中，在培养箱中培养24小时后，细胞融合率达到70％。用5μg/ml放线菌素D处理细胞，分别在0h、2h和4h检测LINC00900的表达水平。
结果如图3C显示，在YTHDF1敲除的GSCs细胞中，LINC00900的表达明显降低，表明YTHDF1可以通过调节其稳定性来影响LINC00900的表达。
实施例4探讨YTHDF1通过上调LINC00900表达影响GSCs增殖、侵袭和自我更新
合成特异性敲低LINC00900的siRNA及对照siRNA，并制备LINC00900的干扰慢病度(慢病毒交由北京欧林格生物科技有限公司合成)。将YTHDF1的过表达慢病毒分别感染GSC-87、GSC-251，随后感染LINC00900的干扰慢病度，得到过表达YTHDF1同时敲除LINC00900的细胞悬液。
表1LINC00900的siRNA的序列
| ID | Target序列信息： |
| si-LINC00900-1 | CCTGGCTAGTCAATCTTTATT |
| si-LINC00900-2 | GAGGGTCCAAGGTTGTTATTT |
| si-LINC00900-3 | GAGGTTACTGTGATGATTAAA |
CCK8结果显示，过表达YTHDF1促进了细胞的增殖能力，而敲除LINC00900则逆转了YTHDF1的增殖作用(图4A)。Transwell实验显示，敲除LINC00900逆转了YTHDF1对GSCs侵袭的影响(图4B)。肿瘤球形成实验显示，敲除LINC00900逆转了YTHDF1对GSCs肿瘤球形成的影响(图4C)。
以上结果说明，YTHDF1通过上调LINC00900的表达来促进GSCs的增殖、侵袭和自我更新。
实施例5探讨LINC00900通过调控miR-1205/STAT3信号轴影响GSCs增殖、侵袭和自我更新
(1)构建LINC00900或STAT33‘UTR野生型(WT)荧光素酶报告基因，并构建突变型(MUT)荧光素酶报告基因，使得miRNA与突变型荧光素酶报告基因无法结合。将荧光素酶报告基因与hsa-miR-1205mimic或对照NC分别在GSCs细胞中共转。采用双荧光素酶报告基因检测试剂盒检测各组荧光素酶的相对活性，验证miR-1205与LINC00900或STAT33’UTR之间的靶向关系。
荧光素酶报告基因实验证实了miR-1205和LINC00900之间的靶标结合关系，LINC00900与miR-1205直接结合(图5A)。进一步证实了，miR-1205与STAT33’UTR直接结合
(2)分别在GSC-87、GSC-251中感染LINC00900过表达慢病毒与对照慢病毒，或LINC00900干扰慢病度与对照干扰慢病度。采用qRT-PCR检测miR-1205的表达水平；采用qRT-PCR和western blot检测STAT3 mRNA和蛋白表达水平
结果如图5B所示，过表达LINC00900显著抑制miR-1205的表达，而敲除LINC00900上调了miR-1205的表达，表明LINC00900负调控miR-1205的表达。采用qRT-PCR和westernblot检测STAT3 mRNA和蛋白表达水平。过表达LINC00900显著上调了STAT3的表达，而敲除LINC00900抑制了STAT3的表达，说明LINC00900正向调控了STAT3的表达。
(3)分别在GSC-87、GSC-251中感染LINC00900过表达慢病毒的同时转染miR-1205mimic。同时在GSCs细胞中过表达LINC00900和miR-1205。结果如图5C和5D显示，miR-1205mimic可以逆转LINC00900对STAT3表达的上调。
(4)采用CCK-8检测对GSCs增殖的影响；Transwell检测对GSCs侵袭的影响；成球实验检测对GSCs自我更新能力的影响。
CCK8结果显示，过表达LINC00900促进了增殖能力，而miR-1205mimic逆转了LINC00900的增殖作用(图5E)。Transwell实验显示，miR-1205mimic逆转了LINC00900对GSCs侵袭的影响(图5F)。肿瘤球形成实验显示，miR-1205mimic逆转了LINC00900对GSCs肿瘤球形成的影响(图5G)。
以上结果证明，LINC00900通过调节miR-1205/STAT3信号轴，促进GSCs的增殖、侵袭和自我更新。
虽然本发明已以较佳实施例公开如上，但其并非用以限定本发明，任何熟悉此技术的人，在不脱离本发明的精神和范围内，都可做各种的改动与修饰，因此本发明的保护范围应该以权利要求书所界定的为准。
Claims (1)
1.YTHDF1在制备LINC00900激动剂中的应用，其特征在于，所述YTHDF1的核苷酸序列如SEQ ID NO.1所示，所述应用不以疾病的治疗为目的；
所述激动剂用于调控LINC00900表达上调，同时促进LINC00900m6A甲基化；
所述激动剂用于制备在细胞实验中促进LINC00900表达的试剂。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310277195.3A CN116327796B (zh) | 2023-03-21 | 2023-03-21 | YTHDF1调控LINC00900 m6A甲基化对胶质瘤干细胞生长和自我更新的影响 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310277195.3A CN116327796B (zh) | 2023-03-21 | 2023-03-21 | YTHDF1调控LINC00900 m6A甲基化对胶质瘤干细胞生长和自我更新的影响 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116327796A CN116327796A (zh) | 2023-06-27 |
| CN116327796B true CN116327796B (zh) | 2024-02-02 |
Family
ID=86890948
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310277195.3A Active CN116327796B (zh) | 2023-03-21 | 2023-03-21 | YTHDF1调控LINC00900 m6A甲基化对胶质瘤干细胞生长和自我更新的影响 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116327796B (zh) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109337980A (zh) * | 2018-11-23 | 2019-02-15 | 中国科学院昆明动物研究所 | 人ythdf1基因的用途 |
| CN111534596A (zh) * | 2020-05-22 | 2020-08-14 | 江西省肿瘤医院(江西省癌症中心) | 胶质瘤恶性进展及生存预后检测分子标志物、替莫唑胺耐药检测靶点及应用 |
| CN112011614A (zh) * | 2020-08-18 | 2020-12-01 | 山东大学齐鲁医院 | Kmt5a在调控胶质瘤干细胞特性及胶质瘤诊治中的应用 |
| CN114317600A (zh) * | 2020-10-12 | 2022-04-12 | 上海君赛生物科技有限公司 | 新型PiggyBac转座子系统及其用途 |
-
2023
- 2023-03-21 CN CN202310277195.3A patent/CN116327796B/zh active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109337980A (zh) * | 2018-11-23 | 2019-02-15 | 中国科学院昆明动物研究所 | 人ythdf1基因的用途 |
| CN111534596A (zh) * | 2020-05-22 | 2020-08-14 | 江西省肿瘤医院(江西省癌症中心) | 胶质瘤恶性进展及生存预后检测分子标志物、替莫唑胺耐药检测靶点及应用 |
| CN112011614A (zh) * | 2020-08-18 | 2020-12-01 | 山东大学齐鲁医院 | Kmt5a在调控胶质瘤干细胞特性及胶质瘤诊治中的应用 |
| CN114317600A (zh) * | 2020-10-12 | 2022-04-12 | 上海君赛生物科技有限公司 | 新型PiggyBac转座子系统及其用途 |
Non-Patent Citations (1)
| Title |
|---|
| 铁死亡相关ｌｎｃＲＮＡ在神经胶质瘤的预后价值分析;陈伟鸿 等;广西科学;第29卷(第2期);结果与分析 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116327796A (zh) | 2023-06-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Newman et al. | Interleukin-13 receptor alpha 2 cooperates with EGFRvIII signaling to promote glioblastoma multiforme | |
| Bae et al. | Hypoxia regulates SOX2 expression to promote prostate cancer cell invasion and sphere formation | |
| Chen et al. | TRAF 6 regulates tumour metastasis through EMT and CSC phenotypes in head and neck squamous cell carcinoma | |
| Du et al. | Long non-coding RNA MAGI2-AS3 inhibits breast cancer cell migration and invasion via sponging microRNA-374a | |
| Zhao et al. | The role of IFITM3 in the growth and migration of human glioma cells | |
| Huang et al. | Expression of NF45 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth | |
| Kim et al. | Tid1 negatively regulates the migratory potential of cancer cells by inhibiting the production of interleukin-8 | |
| CN114686461B (zh) | 去泛素化酶usp45在制备治疗肺鳞癌药物中的应用 | |
| Yang et al. | PARP1 and PRC2 double deficiency promotes BRCA‐proficient breast cancer growth by modification of the tumor microenvironment | |
| Yang et al. | Gain-of-function E76K-mutant SHP2 promotes cell proliferation, metastasis, and tumor growth in glioblastoma through activation of the ERK/CREB pathway | |
| CN109055374B (zh) | 特异性抑制OCT1基因表达的shRNA及应用 | |
| Fang et al. | Circ_0002099 is a novel molecular therapeutic target for bladder cancer | |
| CN116327796B (zh) | YTHDF1调控LINC00900 m6A甲基化对胶质瘤干细胞生长和自我更新的影响 | |
| Lee et al. | CXCL1 confers a survival advantage in Kaposi's sarcoma‐associated herpesvirus‐infected human endothelial cells through STAT3 phosphorylation | |
| CN112359039A (zh) | 靶向沉默BRD4基因表达的shRNA序列及其用途 | |
| CN114703190B (zh) | 一种靶向抑制KIAA1429基因表达的ShRNA在慢性髓细胞白血病中的应用 | |
| CN114032236B (zh) | 一种TMEM2的shRNA及其应用 | |
| Seol et al. | The guanine nucleotide exchange factor SWAP-70 modulates the migration and invasiveness of human malignant glioma cells | |
| Li et al. | Reduced expression of Jumonji AT-rich interactive domain 2 (JARID2) in glioma inhibits tumor growth in vitro and in vivo | |
| Teng et al. | L-Plastin Promotes Gastric Cancer Growth and Metastasis in a Helicobacter pylori cagA-ERK-SP1–Dependent Manner | |
| Wu et al. | MSX2 inhibits the growth and migration of osteosarcoma cells by repressing SOX2 | |
| CN110538179B (zh) | Yg1702在制备aldh18a1特异性抑制剂中的应用 | |
| CN112034183A (zh) | 影响mdk基因调节胶质瘤迁移和侵袭的分子机制及应用 | |
| CN110305962A (zh) | DKC1与HIF-1α在协同治疗结直肠癌中的应用 | |
| Li et al. | MicroRNA-1298-5p inhibits cell proliferation and invasion of bladder cancer via downregulating connexin 43 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |