Comprehensive analysis of ubiquitin‐specific protease 1 reveals its importance in hepatocellular carcinoma

Objectives In this study, we comprehensively analysed the role of ubiquitin‐specific protease 1(USP1) in hepatocellular carcinoma (HCC) using data from a set of public databases. Materials and Methods We analysed the mRNA expression of USP1 in HCC and subgroups of HCC using Oncomine and UALCAN. Survival analysis of USP1 in HCC was conducted with the Kaplan‐Meier Plotter database. The mutations of USP1 in HCC were analysed using cBioPortal and the Catalogue of Somatic Mutations in Cancer database. Differential genes correlated with USP1 and WD repeat domain 48 (WDR48) were obtained using LinkedOmics. USP1 was knocked down with small interfering RNA (siRNA) or pharmacologically inhibited by ML‐323 in MHCC97H or SK‐Hep‐1 cell lines for function analysis. Results High USP1 expression predicted unfavourable overall survival in HCC patients. USP1 showed positive correlations with the abundances of macrophages and neutrophils. We identified 98 differential genes that were positively correlated with both USP1 and WDR48. These genes were mainly involved in the cell cycle, aldosterone synthesis and secretion and oestrogen signalling pathways. Interactions between USP1 and WDR 48 were confirmed using co‐immunoprecipitation. USP1 knockdown or ML‐323 treatment reduced the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E1. Conclusions Overall, USP1 is a promising target for HCC treatment with good prognostic value. USP1 and WDR48 function together in regulating cancer cell proliferation via the cell cycle. Ubiquitin‐specific protease 1 (USP1) is significantly overexpressed in hepatocellular carcinoma (HCC). High expression of USP1 predicts poor survival of HCC patients. In general, USP1 functions together with its cofactor WD repeat domain 48 (WDR48). Here, we find that WDR48 shows positive correlation with USP1 in HCC. Ninety‐eight coexpressed genes are mainly involved in the cell cycle, aldosterone synthesis and secretion and oestrogen signalling pathways. USP1 interacts with WDR48 in MHCC97H and SK‐Hep‐1 cells. USP1 knockdown or ML‐323 treatment decreases cell proliferation, and reduces expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E1. Overall, USP1 is a novel therapeutic target for HCC treatment with good prognostic value. USP1 and WDR48 function together in regulating cancer cell proliferation via the cell cycle.