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

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.