RETRACTED ARTICLE: RNA m6A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail

Xinyao Lin, Guoshi Chai, Yingmin Wu, Jiexin Li, Feng Chen, Jianzhao Liu, Guanzheng Luo, Jordi Tauler, Jun Du, Shuibin Lin, Chuan He and Hongsheng Wang ()
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Xinyao Lin: Sun Yat-sen University
Guoshi Chai: Sun Yat-sen University
Yingmin Wu: Sun Yat-sen University
Jiexin Li: Sun Yat-sen University
Feng Chen: Sun Yat-sen University
Jianzhao Liu: The University of Chicago
Guanzheng Luo: Sun Yat-sen University
Jordi Tauler: The University of Chicago
Jun Du: Sun Yat-sen University
Shuibin Lin: Sun Yat-sen University
Chuan He: The University of Chicago
Hongsheng Wang: Sun Yat-sen University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09865-9

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