N6-Methyladenosine Regulates The Expression And Secretion Of Tgf Beta 1 To Affect The Epithelial-Mesenchymal Transition Of Cancer Cells

N6-methyladenosine (m(6)A) is the most abundant modification on eukaryotic mRNA, which regulates all steps of the mRNA life cycle. An increasing number of studies have shown that m(6)A methylation plays essential roles in tumor development. However, the relationship between m(6)A and the progression of cancers remains to be explored. Here, we reported that transforming growth factor-beta (TGF beta 1)-induced epithelial-mesenchymal transition (EMT) was inhibited in methyltransferase-like 3 (METTL3) knockdown (Mettl3(Mut/-)) cells. The expression of TGF beta 1 was up-regulated, while self-stimulated expression of TGF beta 1 was suppressed in Mettl3(Mut/-) cells. We further revealed that m(6)A promoted TGFB1 mRNA decay, but impaired TGFB1 translation progress. Besides this, the autocrine of TGF beta 1 was disrupted in Mettl3(Mut/-) cells via interrupting TGF beta 1 dimer formation. Lastly, we found that Snail, which was down-regulated in Mettl3(Mut/-) cells, was a key factor responding to TGF beta 1-induced EMT. Together, our research demonstrated that m(6)A performed multi-functional roles in TGF beta 1 expression and EMT modulation, suggesting the critical roles of m(6)A in cancer progression regulation.