A20 promotes OPN ubiquitination and degradation to inhibit cell growth and invasion in human hepatocellular carcinoma.

Abnormal osteopontin (OPN) expression has been implicated in hepatocellular carcinoma (HCC) progression. In this study, we assessed the prognostic value and biological functions of OPN in HCC. We also identified that A20 interacts with OPN and promotes OPN ubiquitination and protein degradation through the ubiquitin-proteasome system. The reduction in OPN levels induced by A20 attenuates OPN-associated proliferative and migratory phenotypes in HCC cells. Notably, advanced HCC tissues exhibited elevated OPN levels, while A20 expression showed variable patterns in clinical samples. In the clinical cohort, high OPN expression was associated with poorer overall survival, while high A20 expression was also unexpectedly associated with unfavorable prognosis. Combined analysis of OPN and A20 expression provided complementary prognostic stratification for HCC patients. Consequently, our results reveal a mechanism involving OPN ubiquitination and suggest that the OPN/A20 expression profile may provide prognostic stratification for patients after HCC resection. Considering the significance of OPN expression in HCC, our research also provides insights into potential therapeutic strategies for HCC.