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

Abstract Background Although the modification of N6-methyladenosine is involved in the progression of a variety of cancers, the associated regulatory mechanism underlying the progression of choroidal melanoma remains poorly understood. Methods In this study, we aimed to investigate the mechanism of N6-methyladenosine in the pathogenesis of choroidal melanoma. The expression level of methyltransferase-like 14 in choroidal melanoma tissues was determined using western blot analysis and immunohistochemistry, and compared with that in normal choroidal tissues. Next, 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, protein expression of factors related to the Wnt/β-catenin signaling pathway was evaluated by western blot analysis. Results Methyltransferase-like 14 was upregulated in choroidal melanoma tissues in comparison with that in normal choroidal tissues. Overexpression and knockdown of methyltransferase-like 14 enhanced and 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, and this effect was dependent on N6-methyladenosine. Additionally, the Wnt/β-catenin signaling pathway was activated by methyltransferase-like 14 in choroidal melanoma cells. Conclusions 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.