CN114015685B - 特异性修饰的脱氧核苷酸短链及其应用 - Google Patents
特异性修饰的脱氧核苷酸短链及其应用 Download PDFInfo
- Publication number
- CN114015685B CN114015685B CN202111077958.7A CN202111077958A CN114015685B CN 114015685 B CN114015685 B CN 114015685B CN 202111077958 A CN202111077958 A CN 202111077958A CN 114015685 B CN114015685 B CN 114015685B
- Authority
- CN
- China
- Prior art keywords
- cells
- rna
- cancer cells
- telomerase
- short chain
- 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
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
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/33—Chemical structure of the base
- C12N2310/334—Modified C
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/33—Chemical structure of the base
- C12N2310/335—Modified T or U
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/33—Chemical structure of the base
- C12N2310/336—Modified G
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种特异性修饰的脱氧核苷酸短链,其特征在于其核苷酸序列为:5’‑CGGGGACTCGCTCCGTTCCTCTTC‑3’,其中5’端的前三个碱基CGG、3’端的最后三个碱基TTC进行硫代修饰,本发明的核苷酸短链通过特异性的结合端粒酶RNA后,细胞内RNaseH能够识别DNA‑RNA杂链,并能够降解其中的RNA链,因此也就可以降解细胞内的端粒RNA,致使细胞内的端粒酶无法发挥作用,最终导致肿瘤细胞的凋亡。该发明已经可成功应用于人胃癌细胞、宫颈癌细胞、肝癌细胞、乳腺癌、JurkatT细胞的端粒酶RNA的敲低,并且观察到了显著的细胞凋亡现象,表明该核苷酸短链具有广谱而有效的抗肿瘤前景。
Description
技术领域
本发明涉及一种特异性修饰的脱氧核苷酸短链及其应用。
背景技术
端粒(Telomere)是存在于真核细胞线性染色体末端的一小段DNA-蛋白质复合体,构成了特殊的“帽子”结构,主要功能是保持染色体的完整性与稳定性,是维持细胞正常生理功能所必须的特殊DNA序列。在正常细胞中,细胞每分裂一次,染色体顶端的端粒就缩短一次,随着细胞分裂次数的增加,其端粒磨损越多,细胞寿命越短。当端粒不能再缩短时,细胞就无法继续分裂了,进而开始走向衰老或者凋亡途径。因此,端粒被科学家们视为“生命时钟”。
然而,癌细胞具有无限增殖的能力,这些细胞在不断的复制过程中,其端粒没有缩短,更没有进入衰老或者细胞凋亡途径。科学家们研究发现恶性肿瘤细胞能够维持其端粒完整性的主要原因是肿瘤细胞具有高活性的端粒酶。比如,目前已经发现的端粒酶阳性的肿瘤有:卵巢癌、淋巴瘤、急性白血病、乳腺癌、结肠癌、肺癌等。
端粒酶是一种特殊的逆转录酶,由RNA和逆转录酶(TERT)组成一个RNA蛋白复合体。逆转录酶(TERT)是以自身携带的RNA为模板,合成端粒重复序列,加到新合成DNA链末端,负责端粒的延长。因此,端粒酶可以把DNA复制损失的端粒填补起来,藉由把端粒修复延长,可以让端粒不会因细胞分裂而有所损耗,使细胞分裂的次数无限增加。正是基于这种机制,癌细胞就能够依赖其细胞内高活性的端粒酶使自身的DNA在复制过程中不被缩短。
因为端粒酶在肿瘤细胞中具有高活性,而在绝大部分正常细胞中不具有活性。因此针对端粒酶活性的治疗方案能够选择性的杀死肿瘤细胞,显著降低对正常细胞的毒性。目前,对于抑制端粒酶活性的药物研发中,主要集中在针对于小分子抑制剂的研发。例如,核苷类逆转录酶抑制剂ddG和AZT,通过与单核苷酸三磷酸竞争性结合端粒酶,抑制端粒酶的逆转录过程。
然而,目前针对抑制端粒RNA在细胞内的含量从而抑制端粒酶活性的相关研究还比较缺乏。因此,本发明从抑制端粒RNA入手,设计了一种特异性结合端粒RNA的DNA序列,这个DNA-RNA杂链能够在细胞内RNase H的作用下,降解其中的RNA,从而使端粒RNA在细胞内的含量显著下降,导致端粒酶失去自身RNA模板,最终不能够延长端粒进而引起细胞凋亡。
发明内容
本发明的目的是提供一种特异性修饰的脱氧核苷酸短链,可以使端粒RNA在细胞内的含量显著下降。
本发明采取的技术方案为:一种特异性修饰的脱氧核苷酸短链,其特征在于其核苷酸序列为:5’-CGGGGACTCGCTCCGTTCCTCTTC-3’,其中5’端的前三个碱基CGG、3’端的最后三个碱基TTC进行硫代修饰,修饰结构如下:
本发明还公开了上述的特异性修饰的脱氧核苷酸短链在敲低端粒RNA中的应用。
优选的,将特异性修饰的脱氧核苷酸短链转染到目标细胞中。
本发明还公开了上述的特异性修饰的脱氧核苷酸短链在制备治疗杀伤癌症细胞的药物中的应用。
优选的,所述癌症细胞为胃癌细胞、宫颈癌细胞、肝癌细胞、乳腺癌或Jurkat T细胞。
本发明具有以下有益效果:
1、本发明的核苷酸短链经硫代修饰后,序列的前三个碱基与后三个碱基中磷酸二酯键的OH被S所取代,变成不是典型的3’-5’磷酸二酯键。因此,可以有效防止细胞内的DNA外切酶对该片段的降解,延长该片段在细胞内的作用时间。硫代修饰又基本上不影响碱基之间的互补配对,所以这种修饰方式不会对DNA-RNA结合亲和力造成影响。
2、本发明的核苷酸短链通过特异性的结合端粒酶RNA后,细胞内RNaseH能够识别DNA-RNA杂链,并能够降解其中的RNA链,因此也就可以降解细胞内的端粒RNA,致使细胞内的端粒酶无法发挥作用,最终导致肿瘤细胞的凋亡。该发明已经可成功应用于人胃癌细胞、宫颈癌细胞、肝癌细胞、乳腺癌、Jurkat T细胞的端粒酶RNA的敲低,并且观察到了显著的细胞凋亡现象,表明该核苷酸短链具有广谱而有效的抗肿瘤前景。
附图说明
图1:real-time PCR检测细胞转染不同的F1-F6片段之后,端粒RNA的表达情况。
图2:real-time PCR检测F5片段在不同肿瘤细胞内敲低端粒RNA的情况。
图3:当各种不同类型的癌细胞的端粒RNA被敲低后,Annexin V检测细胞的早期凋亡情况。
图4:当A549(肺癌)细胞的端粒RNA被敲低后,western blot检测细胞凋亡通路的激活情况。
图5:当Jurkat(白血病)细胞的端粒RNA被敲低后,western blot检测细胞凋亡通路的激活情况。
具体实施方式
为更进一步阐述本发明为实现预定发明目的所采取的技术手段及功效,以下结合附图及较佳实施例,对依据本发明的具体实施方式、结构、特征及其功效,详细说明如后。
实施例1
我们采用MGC-803细胞进行初步研究,将细胞接种于6孔板,用含有10%FBS的DMEM培养基培养,待细胞长至密度为30%-50%时进行转染,37℃预热opti-MEM I和培养基。取3μL Lipo 2000稀释至250μL opti-MEM I中,轻轻吹打均匀,室温静置5分钟。取2μL 100mM对应的F1-F6片段中的其中一种,稀释至250μL的opti-MEM I,轻轻吹打均匀;将稀释的Lipo2000和反义核苷酸链轻轻混匀,室温静置20min。吸去六孔板中待转染的细胞的培养基,换上新鲜预热的培养基。静置20min后将混合物逐滴加入六孔板中,加入1.5ml的完全培养基,使反义核苷酸最终的转染浓度为100nM。6小时后换液,待48小时后去除上清,收集细胞进行相应的实验。
针对端粒RNA不同位点设计反义核苷酸链F1-F6,F1序列为:5’-CTCCCAGGCCCACCCTCCGCAACCC-3’,F2序列为:5’-5’-GCCGAGGCTTTTCCGCCCGCT-3’,F3序列为:5’-GGGGCGAACGGGCCAGCAGC-3’,F4序列为:5’-CAACTCTTCGCGGTGGCAGTGGGT-3’,F5序列为:5’-CGGGGACTCGCTCCGTTCCTCTTC-3’,F6:序列为5’-CGTCCCACAGCTCAGGGAATCGCG-3’,以上所有6个片段均进行前三个碱基和后三个碱基的硫代修饰;将反义核苷酸链转染到细胞24h后提取细胞内的总RNA,real-time PCR检测端粒RNA的含量。试验结果如图1所示,结果表明,F5抑制端粒RNA在细胞内的含量的效果最明显。F5的序列5’-CGGGGACTCGCTCCGTTCCTCTTC-3’,其中5’端的前三个碱基CGG、3’端的最后三个碱基TTC进行硫代修饰。
实施例2
选择hela(宫颈癌)、SK-BR-3(乳腺癌)、SMMC-7721(肝癌)、HGC-27(胃癌)、A549(肺癌)、Jurkat(白血病)这6种肿瘤细胞,将F5转染到细胞内,以未转染任何核苷酸短链的细胞为对照,转染48h后收集细胞,Real-time PCR检测细胞内端粒RNA含量的变化,结果如图2所示,图2中对照组为白色柱子,实验组为黑色柱子。可以明显观察到各个细胞内端粒RNA的含量均显著降低,表明F5在不同的肿瘤细胞内均具有降解端粒RNA的作用。
Annexin V检测细胞凋亡方法:胰酶消化细胞,不要丢弃任何液体,300g,4℃水平离心10min收集细胞。4℃预冷的PBS清洗一次;将5 xAnnexin V binding buffer用双蒸水稀释至1x工作浓度,每个样品吸取100μL 1xAnnexin V binding buffer轻轻重悬细胞;向样品中加入5μL Alexa Flour 488 Annexin V和1μL PI(工作浓度为100ug/ml,用1xAnnexin V binding buffer稀释),室温避光孵育15min;向样品中加入400μL 1xAnnexinV binding buffer停止上述反应。将待测样品存于冰上,于流式细胞仪上进行检测。用Annexin V检测当端粒RNA被降解之后,细胞的早期凋亡情况。结果如图3所示,图3中对照组为白色柱子,实验组为黑色柱子。表明当细胞内的端粒RNA被显著降低之后,各个不同类型肿瘤细胞的早期凋亡情况显著上升,表明F5能够显著诱导细胞凋亡,具有潜在的广谱抗肿瘤作用。
实施例3
选择A549(肺癌)细胞,将F5转染到细胞内,以未转染任何核苷酸短链的细胞为对照,转染48h后收集细胞,检测细胞凋亡通过中的关键调控蛋白Caspase 3、p53、Bax、Bcl-2的表达情况。结果如图4所示。结果表明当细胞内的端粒RNA被显著降低之后,凋亡调控蛋白的表达发生显著的变化,凋亡信号通路被激活。
实施例4
选择Jurkat(白血病)细胞,将F5转染到细胞内,以未转染任何核苷酸短链的细胞为对照,转染48h后收集细胞,检测细胞凋亡通过中的关键调控蛋白Caspase 3、p53、Bax、Bcl-2的表达情况。结果如图5所示。结果同样表明当细胞内的端粒RNA被显著降低之后,凋亡调控蛋白的表达发生显著的变化,凋亡信号通路被激活。
以上所述,仅是本发明的较佳实施例而已,并非对本发明作任何形式上的限制,虽然本发明已以较佳实施例揭示如上,然而并非用以限定本发明,任何本领域技术人员,在不脱离本发明技术方案范围内,当可利用上述揭示的技术内容做出些许更动或修饰为等同变化的等效实施例,但凡是未脱离本发明技术方案内容,依据本发明的技术实质对以上实施例所作的任何简介修改、等同变化与修饰,均仍属于本发明技术方案的范围内。
Claims (4)
1.一种特异性修饰的脱氧核苷酸短链,其特征在于其核苷酸序列为:
5’-CGGGGACTCGCTCCGTTCCTCTTC-3’,其中5’端的前三个碱基CGG、3’端的最后三个碱基TTC进行硫代修饰,修饰结构如下:
2.权利要求1所述的特异性修饰的脱氧核苷酸短链在非诊断和治疗目的的敲低端粒RNA中的应用。
3.根据权利要求2所述的应用,其特征在于其步骤为:将特异性修饰的脱氧核苷酸短链转染到目标细胞中。
4.权利要求1所述的特异性修饰的脱氧核苷酸短链在制备治疗杀伤癌症细胞的药物中的应用,所述癌症细胞为胃癌细胞、宫颈癌细胞、肝癌细胞、乳腺癌或Jurkat T细胞。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111077958.7A CN114015685B (zh) | 2021-09-15 | 2021-09-15 | 特异性修饰的脱氧核苷酸短链及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111077958.7A CN114015685B (zh) | 2021-09-15 | 2021-09-15 | 特异性修饰的脱氧核苷酸短链及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114015685A CN114015685A (zh) | 2022-02-08 |
CN114015685B true CN114015685B (zh) | 2023-10-13 |
Family
ID=80054098
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111077958.7A Active CN114015685B (zh) | 2021-09-15 | 2021-09-15 | 特异性修饰的脱氧核苷酸短链及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114015685B (zh) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2003264633A1 (en) * | 1998-04-20 | 2004-01-08 | Ribozyme Pharmaceuticals, Inc. | Nucleic Acid Molecules with Novel Chemical Compositions Capable of Modulating Gene Expression |
WO2004029212A2 (en) * | 2002-09-25 | 2004-04-08 | University Of Massachusetts | In vivo gene silencing by chemically modified and stable sirna |
CN102311956A (zh) * | 2011-09-20 | 2012-01-11 | 浙江大学 | 一种特异性碱基修饰反义核苷酸链及其应用 |
CN103060323A (zh) * | 2012-08-03 | 2013-04-24 | 浙江大学 | 一种反义核苷酸链及其在制备治疗胃癌的药物中的应用 |
WO2015148624A1 (en) * | 2014-03-25 | 2015-10-01 | Ajit Kumar | Blocking hepatitis c virus infection associated liver tumor development with hcv-specific antisense rna |
CN107058309A (zh) * | 2017-05-11 | 2017-08-18 | 北京梓熙生物科技有限公司 | 一种硫代修饰引物及应用该引物的snp检测方法 |
CN108486231A (zh) * | 2018-05-25 | 2018-09-04 | 山东维真生物科技有限公司 | 用于检测人类cyp2c19基因多态性的引物探针组合物、试剂盒及应用 |
-
2021
- 2021-09-15 CN CN202111077958.7A patent/CN114015685B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2003264633A1 (en) * | 1998-04-20 | 2004-01-08 | Ribozyme Pharmaceuticals, Inc. | Nucleic Acid Molecules with Novel Chemical Compositions Capable of Modulating Gene Expression |
WO2004029212A2 (en) * | 2002-09-25 | 2004-04-08 | University Of Massachusetts | In vivo gene silencing by chemically modified and stable sirna |
CN102311956A (zh) * | 2011-09-20 | 2012-01-11 | 浙江大学 | 一种特异性碱基修饰反义核苷酸链及其应用 |
CN103060323A (zh) * | 2012-08-03 | 2013-04-24 | 浙江大学 | 一种反义核苷酸链及其在制备治疗胃癌的药物中的应用 |
WO2015148624A1 (en) * | 2014-03-25 | 2015-10-01 | Ajit Kumar | Blocking hepatitis c virus infection associated liver tumor development with hcv-specific antisense rna |
CN107058309A (zh) * | 2017-05-11 | 2017-08-18 | 北京梓熙生物科技有限公司 | 一种硫代修饰引物及应用该引物的snp检测方法 |
CN108486231A (zh) * | 2018-05-25 | 2018-09-04 | 山东维真生物科技有限公司 | 用于检测人类cyp2c19基因多态性的引物探针组合物、试剂盒及应用 |
Non-Patent Citations (1)
Title |
---|
全硫代反义寡核苷酸对卵巢癌细胞生长抑制作用;刘学;单伟;曾瑞霞;房艳;李德华;秦书俭;;中国实用医药(第08期);全文 * |
Also Published As
Publication number | Publication date |
---|---|
CN114015685A (zh) | 2022-02-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Lv et al. | Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury | |
Lissoni et al. | Efficacy of cancer chemotherapy in relation to the pretreatment number of lymphocytes in patients with metastatic solid tumors | |
Ma et al. | Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a | |
Kendellen et al. | Canonical and non-canonical NF-κB signaling promotes breast cancer tumor-initiating cells | |
Salvatore et al. | A cell proliferation and chromosomal instability signature in anaplastic thyroid carcinoma | |
EP3199165B1 (en) | Methods and compositions for the specific inhibition of kras by asymmetric double-stranded rna | |
EP2756845B1 (en) | Methods and compositions for the specific inhibition of KRAS by asymmetric double-stranded RNA | |
Engelbert et al. | The ubiquitin ligase APCCdh1 is required to maintain genome integrity in primary human cells | |
Chen et al. | Inhibition of EGR1 inhibits glioma proliferation by targeting CCND1 promoter | |
EP1786905B1 (en) | Small interfering rna molecules against ribonucleotide reductase and uses thereof | |
Adamo et al. | RYK promotes the stemness of glioblastoma cells via the WNT/β-catenin pathway | |
Song et al. | Mi R‐370 and mi R‐373 regulate the pathogenesis of osteoarthritis by modulating one‐carbon metabolism via SHMT‐2 and MECP‐2, respectively | |
EP2316491A1 (en) | Cell proliferation inhibitor | |
Gao et al. | MicroRNA-222 influences migration and invasion through MIA3 in colorectal cancer | |
Chen et al. | Long non-coding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) alleviates osteoarthritis progression by regulation of extracellular matrix homeostasis | |
Wei et al. | Knocking down cyclin D1b inhibits breast cancer cell growth and suppresses tumor development in a breast cancer model | |
Liu et al. | Hypoxia‐induced polypoid giant cancer cells in glioma promote the transformation of tumor‐associated macrophages to a tumor‐supportive phenotype | |
Xing et al. | Mesenchymal stroma/stem‐like cells of GARP knockdown inhibits cell proliferation and invasion of mouse colon cancer cells (MC38) through exosomes | |
Li et al. | Expression of interleukin‐12 by adipose‐derived mesenchymal stem cells for treatment of lung adenocarcinoma | |
Maggisano et al. | Human telomerase reverse transcriptase in papillary thyroid cancer: gene expression, effects of silencing and regulation by BET inhibitors in thyroid cancer cells | |
Guo et al. | Hypoxia-induced neuronal activity in glioma patients polarizes microglia by potentiating RNA m6A demethylation | |
CN114015685B (zh) | 特异性修饰的脱氧核苷酸短链及其应用 | |
Guo et al. | Neuronal activity promotes glioma progression by inducing proneural-to-mesenchymal transition in glioma stem cells | |
Liu et al. | Cooperative disengagement of Fas and intercellular adhesion molecule-1 function in neoplastic cells confers enhanced colonization efficiency | |
Khakpoor-Koosheh et al. | MicroRNA-124 enhances T cells functions by manipulating the lactic acid metabolism of tumor cells |
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 |