METTL3 promotes choriocarcinoma progression by activating the miR‐935/GJA1 pathway in an m6A‐dependent manner

Abstract

AbstractThe emerging role of microRNA‐935 (miR‐935) in modulating cancer progression has been recognized. However, its role in regulating choriocarcinoma (CCA) development and progression remains unknown. The present work aims to reveal the effect of miR‐935 on CCA cell tumor properties and the related mechanism. The RNA expression of methyltransferase 3, N6‐adenosine‐methyltransferase complex catalytic subunit (METTL3), miR‐935, and gap junction protein alpha 1 (GJA1) was detected by quantitative real‐time polymerase chain reaction. Protein expression of GJA1, Ki67, and METTL3 was measured by western blotting and immunohistochemistry assays. CCK‐8 and colony formation were used to analyze cell proliferation. Transwell assays were performed to assess cell migration and invasion. Angiogenesis was investigated by tube formation assay. Xenograft mouse model assay was used to determine miR‐935‐mediated effect on tumor formation in vivo. The luciferase reporter assay and RNA pull‐down assay were used to verify the relationship between miR‐935 and GJA1. MeRIP assay was used to analyze the m6A methylation of pri‐miR‐935. MiR‐935 expression was significantly upregulated in CCA tissues and cells when compared with control groups. MiR‐935 overexpression promoted CCA cell proliferation, migration, invasion, and tube formation and tumor tumorigenesis in vitro and in vivo, but miR‐935 knockdown showed the opposite effects. In addition, miR‐935 targeted GJA1 and mediated CCA cell tumor properties by negatively regulating GJA1 expression. METTL3 promoted miR‐935 maturation by inducing m6A methylation of pri‐miR‐935, and its overexpression contributed to CCA cell tumor properties through the regulation of miR‐935. METTL3 promoted choriocarcinoma progression by m6A‐dependently activating the miR‐935/GJA1 pathway.