Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells.

Abstract

The roles of RNA m6A modification in carcinogenesis have attracted much interest recently. However, the dysregulation of RNA m6A regulators (writers, readers, and erasers) in nasopharyngeal carcinoma (NPC) has never been reported. In this study, we showed that METTL3, one of the writers, was upregulated in NPC. Functional studies revealed that METTL3 promoted the migration and invasion of NPC cells. However, METTL3 knockdown reversed this effect and inhibited the migration, invasion and metastasis of NPC cells. METTL3 activated the luciferase activity of TOPflash (a reporter for beta-catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of beta-catenin/TCF target genes vimentin and N-cadherin, which are two regulators of epithelial-mesenchymal transition. Moreover, dominant negative beta-catenin blocked the migration and invasion of NPC cells. Further mechanistic studies showed that METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. Moreover, Tankyrase overexpression abrogated the repressive effects of METTL3 silencing on the migration of NPC cells. Collectively, our study demonstrates the oncogenic roles of METTL3 in NPC, and suggests that METTL3 might be a therapeutic target for NPC.