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

Authors Zhai R, Tang F, Gong JH, Zhang J, Lei B, Li B, Wei YC, Liang XS, Tang B, He SQ

Received 20 April 2016

Accepted for publication 6 July 2016

Published 24 November 2016 Volume 2016:9 Pages 6987—6998

DOI https://doi.org/10.2147/OTT.S110985

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor Min Li


Run Zhai,1,2,* Fang Tang,3,* Jianhua Gong,1,2,* Jing Zhang,1,2 Biao Lei,1,2 Bo Li,2 Yangchao Wei,1,2 Xingsi Liang,1 Bo Tang,1,2 Songqing He1,2

1Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, Guangxi, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, People’s Republic of China; 3Pathology Department, Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, People’s Republic of China

*These authors contributed equally to this work

Abstract: 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.

Keywords: hepatocellular carcinoma, USP22, BMI1, EZH2

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