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

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Abstract

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.

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Acknowledgments

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Funding

No funding was received.

Conflict of interest

Gang Hu, Jianwu Yang, Hongwen Zhang, Zhen Huang and Heming Yang declare that they have no conflicts of interest.

Ethical Approval

The procedure of this research was reviewed and approved by Strategic Support Force Characteristic Medical Center.

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Authors and Affiliations

  1. Department of General Surgery, Strategic Support Force Characteristic Medical Center, 9# Anxiang Beili, Chaoyang District, Beijing, 100101, China

    Gang Hu, Jianwu Yang, Hongwen Zhang, Zhen Huang & Heming Yang

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  1. Gang Hu
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Correspondence to Heming Yang.

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Hu, G., Yang, J., Zhang, H. et al. OTUB2 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by PJA1 Deubiquitylation. Cel. Mol. Bioeng. 15, 281–292 (2022). https://doi.org/10.1007/s12195-022-00720-4

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