基因敲除
癌变
脱甲基酶
生物
核糖核酸
干细胞
癌症研究
信使核糖核酸
RNA甲基化
甲基转移酶
甲基化
细胞生物学
小RNA
表观遗传学
基因
遗传学
作者
Qi Cui,Hailing Shi,Peng Ye,Li Li,Qiuhao Qu,Guoqiang Sun,Guihua Sun,Zhike Lu,Yue Huang,Cai‐Guang Yang,Arthur D. Riggs,Chuan He,Yanhong Shi
出处
期刊:Cell Reports
[Elsevier]
日期:2017-03-01
卷期号:18 (11): 2622-2634
被引量:1033
标识
DOI:10.1016/j.celrep.2017.02.059
摘要
RNA modifications play critical roles in important biological processes. However, the functions of N6-methyladenosine (m6A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m6A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase 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. m6A sequencing reveals that knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., ADAM19) with critical biological functions in GSCs. In summary, this study identifies the m6A mRNA methylation machinery as promising therapeutic targets for glioblastoma.
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