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

Abstract

N6 -Methyladenosine (m 6 A) 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, m 6 A modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3 (METTL3) down-regulates m 6 A, impairs the migration, invasion and EMT of cancer cells both in vitro and in vivo. m 6 A-sequencing and functional studies confirm that Snail, a key transcription factor of EMT, is involved in m 6 A-regulated EMT. m 6 A 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 m 6 A-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 m 6 A on regulation of EMT in cancer cells and translation of Snail during this process.

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Cited by papers we hold 34

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• RNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases · 2021
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• Epigenetic regulation of epithelial-mesenchymal transition: focusing on hypoxia and TGF-β signaling · 2020
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• The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs · 2020
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and 14 more

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