生物
癌症研究
小RNA
脱甲基酶
恶性肿瘤
癌变
生物发生
食管癌
TFEB
膀胱癌
癌症
细胞生物学
表观遗传学
基因
遗传学
作者
Pengxiang Chen,Li Song,Ke Zhang,Renchang Zhao,Jianfeng Cui,Wei Zhou,Yuchen Liu,Lin Zhang,Yufeng Cheng
出处
期刊:Oncogene
[Springer Nature]
日期:2021-07-26
卷期号:40 (37): 5600-5612
被引量:34
标识
DOI:10.1038/s41388-021-01966-4
摘要
N6-Methyladenosine (m6A) is the most prevalent epigenetic RNA modification and is vital in regulating malignancies. The roles of m6A modifiers on noncoding RNAs have not been fully investigated in esophageal cancer. By screening all m6A modifiers, ALKBH5 was the most potent member related to patient outcomes and suppressing esophageal cancer malignancy in cell and animal models. It demethylated pri-miR-194-2 and inhibited miR-194-2 biogenesis through an m6A/DGCR8-dependent manner. RAI1, previously considered as a circadian clock transcriptional regulator, was the main target of miR-194-2. It enhanced transcription of Hippo pathway upstream genes by binding to their 3'UTR and suppressed YAP/TAZ nuclear translocation. The ALKBH5/miR-194-2/RAI1 axis was also validated in clinical samples. In addition, the increased malignancy by low ALKBH5 was abolished by the YAP inhibitor verteporfin. Our findings uncover a critical role of ALKBH5 in miRNAs biogenesis and provide novel insight for developing treatment strategies in esophageal cancer.
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