PIAS4, upregulated in hepatocellular carcinoma, promotes tumorigenicity and metastasis.

Protein inhibitor of activated STAT4 (PIAS4) protein has been implicated in regulating various biological activities including protein posttranslational modification, such as SUMOylation. In this study, we explored the roles of PIAS4 in hepatocellular carcinoma (HCC). We analyzed the PIAS4 expression in cancer tissues and paracancerous tissues from 38 HCC patients and its correlation with patients' prognosis. In vitro, PIAS4 was overexpressed or knockdowned in Huh-7 and HepG-2 cells. Then Cell Counting Kit-8 assay, flow cytometry, and Transwell assay were performed to assess cell viability, apoptosis, migration, and invasion, respectively. Furthermore, SUMOylation of AMPKα and NEMO mediated by PIAS4 was investigated. The results showed that the PIAS4 expression was significantly upregulated in cancer tissues and was correlated with poor prognosis in HCC patients. PIAS4 silencing blocked the SUMOylation of AMPKα and NEMO, leading to enhanced cell proliferation, migration, and invasion. In addition, inhibition of AMPKα or NEMO by siRNAs attenuated the effect of PIAS4 silencing on Huh-7 and HepG-2 cells. In summary, our findings suggest that PIAS4 promotes tumorigenicity and metastasis of HCC cells by promoting the SUMOylation of AMPKα and NEMO.