HNRNPC contributes to ccRCC progression by stabilizing AURKB mRNA in an m6A-dependent manner.

Abstract

This study aimed to investigate the expression, biological functions, and underlying mechanisms of HNRNPC in clear cell renal cell carcinoma (ccRCC). The expression of HNRNPC in ccRCC tissues and cell lines was detected. The effects of HNRNPC knockdown and overexpression on ccRCC cell proliferation, migration, and invasion were analyzed using cellular models. The role of HNRNPC in recognizing m6A modifications and regulating AURKB mRNA stability was validated through treatment with the methylation inhibitor STM-245, an actinomycin D stability assay, a dual-luciferase reporter assay, and RNA immunoprecipitation. A nude mouse xenograft model was established for in vivo functional validation. The results showed that HNRNPC was significantly overexpressed in ccRCC tissues and cell lines. Knockdown of HNRNPC suppressed cell proliferation, sphere formation, migration, and invasion, while overexpression promoted these malignant phenotypes. Mechanistically, HNRNPC enhanced the stability and expression of AURKB mRNA by recognizing and binding to m6A modification sites on AURKB mRNA. HNRNPC overexpression reversed the suppression of cellular phenotypes induced by AURKB knockdown. In vivo experiments demonstrated that knockdown of either HNRNPC or AURKB significantly inhibited tumor growth and downregulated Ki-67 expression. In conclusion, HNRNPC contributes malignant progression of ccRCC, at least in part, by recognizing m6A modifications on AURKB mRNA and enhancing its stability, suggesting that the HNRNPC/AURKB axis may serve as a potential therapeutic target for ccRCC.