Ring finger protein 14 promotes proliferation, migration and invasion of hepatoma cells by inhibiting hepatocyte nuclear factor-1α

Abstract

Objective To investigate the effects of ring finger protein 14 (RNF14) overexpression and knockdown on the proliferation and invasion of hepatoma cells and explore the mechanism by which RNF14 promote the occurrence and progression of hepatocellular carcinoma (HCC). Methods We investigated the expression of RNF14 in HCC and adjacent tissues using Gene Expression Profiling Interactive Analysis (GEPIA), and examined its expression in normal human hepatocytes and hepatoma cells using Western blotting. The effects of overexpression and knockdown of RNF14 on the migration and invasion abilities of 2 hepatoma cell lines (Hu7 and 7404) were observed using Transwell chamber migration and invasion assay. The effect of RNF14 knockdown on the proliferation of hepatoma cells 7404 was verified by CCK8 proliferation assay, colony formation assay and subcutaneous xenograft tumor formation in nude mice. The interaction between RNF14 and hepatocyte nuclear factor-1α (HNF1α) was tested with co-immunoprecipitation assay. Results The results of GEPIA and Western blotting showed that the expression of RNF14 was significantly higher in hepatoma tissues and cells than in normal hepatic tissues and hepatocytes (P < 0.05). Transwell chamber invasion and migration assays showed that the migration and invasion abilities of Hu7 cells were increased significantly after overexpression of RNF14 (P < 0.05), and RNF14 knockdown significantly attenuated the migration and invasion ability of hepatoma cells 7404 (P < 0.05). The results of CCK8 proliferation assay, colony formation and subcutaneous xenograft tumor formation in nude mice all demonstrated that RNF14 knockdown significantly inhibited the proliferation of hepatoma cells (P < 0.05). Co-immunoprecipitation confirmed that RNF14 could bind to HNF1α and down-regulate the expression of the latter. Conclusion RNF14 promotes the proliferation, migration and invasion of hepatoma cells through degrading HNF1α, and may thus play an important role in the occurrence and progression of HCC.

Keywords

• ring finger protein 14
• hepatocyte nuclear factor-1alpha
• hepatocellular carcinoma
• cell proliferation
• neoplasm migration
• neoplasm invasion