Abstract
m6A modifications are involved in regulating microRNA (miRNA) processing and maturation, and are associated with tumor development. Therefore, this study was aimed to explore the mechanism of miR-122-5p in regulating hepatocellular carcinoma (HCC) progression. mRNA expression and transfection efficiency were detected by RT-qPCR. Western blot was employed to measure protein level. Cell functions were evaluated through CCK-8 and transwell, respectively. Intracellular m6A levels were analyzed by MeRIP. Dual luciferase reporter gene, RIP and co-IP were applied to verify the binding relationship. Xenograft tumor model was carried out for in vivo validation of miR-122-5p function. We reported that miR-122-5p was clearly lessened in HCC. Functionally, miR-122-5p introduction inhibited the malignant progression of HCC. Mechanistically, METTL14 insertion promoted miR-122-5p maturation by labeling pri-miR-122 with m6A. In addition, miR-122-5p exerted suppressor effects by targeting Lysine acetyltransferase 2 A(KAT2A). Moreover, we also found that KAT2A overexpression limited β-catenin expression through succinylation modification. Finally, animal data also illustrated that miR-122-5p introduction could hinder the growth of HCC tumors in vivo. We revealed the existence of a METTL14/miR-122-5p/KAT2A/β-catenin mechanistic axis in HCC, which has not been reported in the literature. This newly discovered mechanistic axis may provide new ideas for HCC therapy.