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

IF 2.3 4区 医学 Q3 BIOPHYSICS
Gang Hu, Jianwu Yang, Hongwen Zhang, Zhen Huang, Heming Yang
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引用次数: 1

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.

Abstract Image

OTUB2通过PJA1去泛素化促进肝癌细胞增殖和迁移。
最近的研究表明,几种去泛素化酶(DUBs)在肝细胞癌(HCC)的进展中起重要作用,但otubain2 (OTUB2)在HCC中的作用尚不清楚。方法:本研究基于临床样本和公共在线数据库(ENCORI)研究OTUB2在HCC中的表达,并通过体外实验进一步探讨其作用和作用机制。结果:发现OTUB2在HCC组织中表达显著上调,并与HCC患者预后不良相关。功能上,OTUB2过表达可促进肝癌细胞的恶性增殖和转移,而OTUB2敲低则相反。利用两种生物信息学工具,PJA1被鉴定为OTUB2调控的潜在基因。机制上,基于免疫沉淀(IP)和环己亚胺(CHX)测定,发现OTUB2通过去泛素化促进PJA1的稳定。此外,OTUB2缺失对HCC细胞恶性表型的抑制作用可以通过过表达PJA1来逆转。结论:综上所述,我们的研究表明OTUB2可以通过去泛素化提高PJA1的稳定性,从而促进HCC细胞的恶性增殖和迁移。
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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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