METTL14 suppresses the migration and invasion of hepatocellular carcinoma cells by m6A methylation of RPLP2

Fluctuating N(6)-methyladenosine (m6A) levels affect the progression of hepatocellular carcinoma (HCC). METTL14, a m6A methyltransferase, acts as a tumor suppressor in HCC; however, its underlying mechanisms need further clarification. This study aimed to clarify the role of METTL14 in HCC and the underlying molecular mechanism. Cellular behaviors were evaluated using cell counting kit-8, EdU, and Transwell assays. The molecular mechanism was analyzed using methylated RNA binding protein immunoprecipitation, dual-luciferase reporter assay, and RNA stability determination. The results demonstrated that METTL14 expression was decreased in HCC tissues and cells, and its overexpression suppressed cellular proliferation, migration, and invasion. Moreover, RPLP2 was negatively correlated to METTL14, and it was highly expressed in HCC tissues and cells. METTL14 promoted the m6A modification of RPLP2 and reduced its stability, thereby inhibiting malignant behaviors. Besides, YTHDC2 decreased RPLP2 expression and reversed the stability induced by METTL14. In conclusion, METTL14 inhibits HCC progression by regulating the YTHDC2-m6A-RPLP2 axis.