METTL3 promotes the proliferation and invasion of esophageal cancer cells partly through AKT signaling pathway.

Methyltransferase-like 3 (METTL3) is identified as a methyltransferase responsible for N6-methyladenosine (m6A) modification of mRNA, miRNA and lncRNA. Emerging evidences suggest that METTL3 is involved in tumorigenesis and progression of multiple tumor types. However, the functional role of METTL3 in esophageal cancer (EC) remains unclear. We used specific shRNA to down-regulate the METTL3 expression, and used pcDNA3.1-METTL3 cDNA plasmid to up-regulate the METTL3 expression in Eca-109 and KY-SE150 cells. Biological functions of METTL3 were performed by CCK-8, colony formation, apoptosis analysis, transwell and wound healing assays. Finally, an in-depth mechanism study was performed by an AKT inhibitor. METTL3 knockdown reduced the proliferation, clonality, migration and invasion of Eca-109 and KY-SE150 cells, and induced cell apoptosis, which may be mediated by activation of the mitochondrial apoptotic pathway. Further, METTL3 overexpression promoted the proliferation, clonality, migration and invasion of Eca-109 and KY-SE150 cells, and inhibited cell apoptosis. In addition, METTL3 regulated the expression of Wnt/β-catenin and AKT signaling pathway components. A double-effect inhibitor (BEZ235) inhibited AKT and mTOR phosphorylation and hindered the effect of METTL3 overexpression on the proliferation and migration of Eca-109 and KY-SE150 cells. Our data suggest that METTL3 plays a carcinogenic role in human EC progression partially through AKT signaling pathways, suggesting that METTL3 may serve as a potential therapeutic target for EC therapy.