PSMG3 enhances the proliferation and metastasis of hepatocellular carcinoma via inhibiting HDAC6.

Hepatocellular carcinoma (HCC) is one of the most frequent cancers globally, characterized by significant metastasis and poor prognosis. The proteasome is critical to the pathogenesis of HCC; however, its mechanisms are not fully elucidated. Here, we explored the role of Proteasome Assembly Chaperone 3 (PSMG3) during HCC progression. In this research, both a subcutaneous tumorigenesis model and a lung metastasis model were established in nude mice to investigate the impact of PSMG3 on the proliferation and metastasis of HCC cells. Chromatin immunoprecipitation (ChIP) assays and dual-luciferase reporter assays were performed to determine the regulatory role of the transcription factor CEBPA on PSMG3. Moreover, the RNA sequencing and label-free quantitative proteomics were employed to clarify the mechanisms through which PSMG3 enhances HCC progression. The results indicated that PSMG3 promoted the proliferation and metastasis of HCC. Mechanistically, CEBPA bound to the promoter of PSMG3 and enhanced its transcription. PSMG3 exerted its pro-tumorigenic effects on HCC by modulating the expression of Histone deacetylase 6 (HDAC6). In summary, we show that the CEBPA/PSMG3/HDAC6 axis promotes HCC progression and that PSMG3 might represent a promising therapeutic target in HCC.