OTUB2 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by PJA1 Deubiquitylation.

Introduction: Recent studies have revealed that several deubiquitinating enzymes (DUBs) play important roles in hepatocellular carcinoma (HCC) progression, but the roles of Otubain 2 (OTUB2) in HCC remain obscure. Methods: In this study, we investigated the expression of OTUB2 in HCC based on clinical samples and a public online database (ENCORI), and its roles and working mechanisms were further explored by in vitro experiments. Results: It was found that the expression of OTUB2 was significantly up-regulated in HCC tissues, and correlated with poor prognosis of HCC patients. Functionally, the overexpression of OTUB2 could promote malignant proliferation and metastasis of HCC cells, while knockdown of OTUB2 exerted the opposite results. Using two bioinformatics tools, PJA1 was identified as a potential gene regulated by OTUB2. Mechanistically, it was found that OTUB2 promoted the stabilization of PJA1 by deubiquitylation, based on immunoprecipitation (IP) and cycloheximide (CHX) assays. Moreover, the suppressive effects of OTUB2 depletion on the malignant phenotypes of HCC cells could be reversed by overexpressing PJA1. Conclusion: In conclusion, our study indicated that OTUB2 could promote the malignant proliferation and migration of HCC cells by increasing the stability of PJA1 via deubiquitylation.