蜗牛
上皮-间质转换
多形体
下调和上调
N6-甲基腺苷
翻译(生物学)
癌症研究
生物
细胞生物学
癌细胞
转移
信使核糖核酸
癌症
甲基化
核糖核酸
甲基转移酶
核糖体
基因
遗传学
生态学
作者
Xinyao Lin,Guoshi Chai,Yinuo Wu,Jiexin Li,Feng Chen,Jianzhao Liu,Guan‐Zheng Luo,Jordi Tauler,Jie Du,Shuibin Lin,Chuan He,Hongsheng Wang
标识
DOI:10.1038/s41467-019-09865-9
摘要
N6-Methyladenosine (m6A) modification has been implicated in the progression of several cancers. We reveal that during epithelial-mesenchymal transition (EMT), one important step for cancer cell metastasis, m6A modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3 (METTL3) down-regulates m6A, impairs the migration, invasion and EMT of cancer cells both in vitro and in vivo. m6A-sequencing and functional studies confirm that Snail, a key transcription factor of EMT, is involved in m6A-regulated EMT. m6A in Snail CDS, but not 3'UTR, triggers polysome-mediated translation of Snail mRNA in cancer cells. Loss and gain functional studies confirm that YTHDF1 mediates m6A-increased translation of Snail mRNA. Moreover, the upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. Our study highlights the critical roles of m6A on regulation of EMT in cancer cells and translation of Snail during this process.
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