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m(6)A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells
文献类型：期刊论文
| 作者 | Cui, Qi2,3; Shi, Hailing4,5,6; Ye, Peng2; Li, Li2,3; Qu, Qiuhao2; Sun, Guoqiang2; Sun, Guihua; Lu, Zhike4,5,6; Huang, Yue7; Yang, Cai-Guang7
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| 刊名 | CELL REPORTS
 |
| 出版日期 | 2017-03-14 |
| 卷号 | 18期号:11页码:2622-2634 |
| ISSN号 | 2211-1247 |
| DOI | 10.1016/j.celrep.2017.02.059 |
| 文献子类 | Article |
| 英文摘要 | RNA modifications play critical roles in important biological processes. However, the functions of N-6-methyladenosine (m(6)A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m(6)A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyl-transferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal. Moreover, inhibition of FTO suppresses tumor progression and prolongs lifespan of GSC-grafted mice substantially. m(6)A sequencing reveals that knockdown of METTL3 or METTL14 induced changes in mRNA m(6)A enrichment and altered mRNA expression of genes (e. g., ADAM19) with critical biological functions in GSCs. In summary, this study identifies the m(6)A mRNA methylation machinery as promising therapeutic targets for glioblastoma. |
| WOS关键词 | ADENOSYL-L-METHIONINE ; MESSENGER-RNA ; SUSCEPTIBILITY VARIANTS ; SEX DETERMINATION ; CANCER RISK ; NUCLEAR-RNA ; 5' TERMINUS ; EXPRESSION ; N-6-METHYLADENOSINE ; METHYLTRANSFERASE |
| 资助项目 | Herbert Horvitz Family[00000000] ; Sidell Kagan Foundation[00000000] ; California Institute for Regenerative Medicine[TR2-01832] ; California Institute for Regenerative Medicine[RB4-06277] ; California Institute for Regenerative Medicine[TRAN1-08525] ; NIH[RM1HG008935] ; National Cancer Institute of the National Institutes of Health[P30CA33572] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000397330000009 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272741]  |
| 专题 | 药理学第三研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | He, Chuan; Shi, Yanhong |
| 作者单位 | 1.City Hope Natl Med Ctr, Diabetes & Metab Res Inst, Duarte, CA 91010 USA; 2.City Hope Natl Med Ctr, Beckman Res Inst, Dept Dev & Stem Cell Biol, Div Stem Cell Biol Res, Duarte, CA 91010 USA; 3.City Hope Natl Med Ctr, Beckman Res Inst, Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA; 4.Univ Chicago, Howard Hughes Med Inst, Dept Chem, 929 East 57th St, Chicago, IL 60637 USA; 5.Univ Chicago, Howard Hughes Med Inst, Dept Biochem & Mol Biol, 929 East 57th St, Chicago, IL 60637 USA; 6.Univ Chicago, Howard Hughes Med Inst, Inst Biophys Dynam, 929 East 57th St, Chicago, IL 60637 USA; 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cui, Qi,Shi, Hailing,Ye, Peng,et al. m(6)A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells[J]. CELL REPORTS,2017,18(11):2622-2634. |
| APA | Cui, Qi.,Shi, Hailing.,Ye, Peng.,Li, Li.,Qu, Qiuhao.,...&Shi, Yanhong.(2017).m(6)A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells.CELL REPORTS,18(11),2622-2634. |
| MLA | Cui, Qi,et al."m(6)A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells".CELL REPORTS 18.11(2017):2622-2634. |
入库方式： OAI收割
来源：上海药物研究所
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