METTL14 promotes migration and invasion of choroidal melanoma by targeting RUNX2 mRNA via m6A modification.

Abstract

The modification of N6-methyladenosine is involved in the progression of various cancers. This study aimed to clarify its regulatory mechanism in the pathogenesis of choroidal melanoma. Expression of methyltransferase-like 14 in choroidal melanoma or normal choroidal tissues was determined by Western blot and immunohistochemistry. The impacts of methyltransferase-like 14 on invasion and migration of choroidal melanoma cells were determined using functional and animal experiments. The interaction between methyltransferase-like 14 and its downstream target was identified by methylated RNA immunoprecipitation and a dual-luciferase reporter assay. Additionally, Wnt/β-catenin signalling pathway was evaluated by Western blot. Methyltransferase-like 14 was upregulated in choroidal melanoma compared to the normal choroidal tissues. Overexpression or knockdown of methyltransferase-like 14 enhanced or inhibited the invasion and migration of choroidal melanoma cells, respectively, both in vivo and in vitro. Methyltransferase-like 14 directly targeted downstream runt-related transcription factor 2 mRNA, depending on N6-methyladenosine. Additionally, the Wnt/β-catenin signalling pathway was activated by methyltransferase-like 14 in choroidal melanoma cells. Our study identified a novel RNA regulatory mechanism in which runt-related transcription factor 2 was upregulated by enhanced expression of methyltransferase-like 14 via N6-methyladenosine modification, thus facilitating migration and invasion of choroidal melanoma cells.