SAV1, regulated by HERC4, inhibits the proliferation, migration, and invasion of hepatocellular carcinoma

BACKGROUND: Hepatic carcinoma is one of the most malignant cancers worldwide. Salvador 1 (SAV1) plays a key role in a variety of human carcinogenesis. This study investigated the role of SAV1 and HERC4 in hepatocellular carcinoma (HCC). METHODS: SAV1 and HERC4 expressions in HCC tissues were examined using RT-qPCR assay. The regulatory effect of HERC4 on SAV1 was verified by co-immunoprecipitation (Co-IP), RT-qPCR, Western blot, and immunofluorescent assays in HEP3B and Huh 7 cell lines. In addition, functional experimental verification was performed through Edu staining, colony formation, and Transwell assay. Finally, Xenograft tumor model was finally used in nude mice. RESULTS: Clinical features showed significant difference with SAV1 and HERC4 expression. HERC4 was found to be upregulated, while SAV1 was downregulated in HCC. Patients with high HERC4 or low SAV1 had a worse prognosis. Results showed that HERC4 could notably decreased the expression level of SAV1 in HCC cells. Our results showed that overexpression HERC4 could reverse the inhibitory effects of SAV1 on HCC cell proliferation, migration, and invasion. SAV1 overexpression repressed tumor growth and enhance caspase 3 expression. CONCLUSION: SAV1 can be directly downregulated by HERC4, indicating that the HERC4/SAV1 axis might have great promise for targeted therapies of HCC.