Published on May 6, 2019 in Nat Commun volume 10(1).
PubMed ID: 31061416
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.