RNA m6A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail

作     者：Xinyao Lin Guoshi Chai Yingmin Wu Jiexin Li Feng Chen Jianzhao Liu Guanzheng Luo Jordi Tauler Jun Du Shuibin Lin Chuan He Hongsheng Wang 

作者机构：Guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical Sciences Sun Yat-sen University Guangzhou Guangdong 510006 China. MOE Key Laboratory of Gene Function and Regulation School of Life Sciences Sun Yat-sen University Guangzhou Guangdong 510275 China. Department of Chemistry Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics The University of Chicago 929 East 57th Street Chicago IL 60637 USA. MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang 310027 China. Department of Rehabilitation Medicine Center for Translational Medicine The First Affiliated Hospital Sun Yat-sen University Guangzhou China. Guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical Sciences Sun Yat-sen University Guangzhou Guangdong 510006 China. whongsh@***. 

出 版 物：《Nature communications》 

年 卷 期：2019年第10卷第1期

页      面：2065页

学科分类：07[理学] 08[工学] 

摘      要：N6-Methyladenosine (mA) 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, mA modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3 (METTL3) down-regulates mA, impairs the migration, invasion and EMT of cancer cells both in vitro and in vivo. mA-sequencing and functional studies confirm that Snail, a key transcription factor of EMT, is involved in mA-regulated EMT. mA 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 mA-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 mA on regulation of EMT in cancer cells and translation of Snail during this process.