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Recent studies have shown that deubiquitination plays a key role in tumor progression, metastasis, resistance to chemotherapy drugs, and prognosis. In this study, we investigated the effects of the deubiquitinating enzyme USP22 on the expression of the drug-resistance genes BMI1 and EZH2 in hepatocellular carcinoma (HCC) and on prognosis. Downregulation of USP22 expression with interference ribonucleic acid in resistant HCC cell lines with high USP22 expression resulted in decreased BMI1 expression, but had no effect on EZH2 expression. USP22, BMI1, and EZH2 were highly expressed in HCC tissue, and the expression levels were positively correlated with tumor grade and clinical stage. Correlation analysis showed that USP22 expression was positively correlated with that of BMI1. Kaplan-Meier analysis showed that high levels of USP22 and BMI1 expression were associated with poor overall survival and relapse-free survival in all of the cases and in patients treated with transcatheter arterial chemoembolization. These results suggested that high levels of USP22 expression played an important role in drug resistance to chemotherapeutic drugs in HCC patients by upregulating the expression of BMI1; therefore, coexpression of USP22 and BMI1 may become a new predictor for HCC prognosis and may help guide clinical treatment.

The relationship between the expression of USP22, BMI1, and EZH2 in hepatocellular carcinoma and their impacts on prognosis