title: Hepatitis B Virus X Protein Stimulates Proliferation, Wound Closure and Inhibits Apoptosis of HuH-7 Cells via CDC42.
abstract: Chronic hepatitis B virus (HBV) infection has been considered as the major cause of hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) has been reported to be oncogenic. The underlying mechanisms of HBV-related HCC are not fully understood, and the role played by the HBx protein in HBV induced carcinogenesis remains controversial. CDC42, a member of the Rho GTPase family, has been reported to be overexpressed in several different cancers, including HBV-related HCC. However, the specific role of CDC42 in HCC development remains unclear. Here, we investigated the cellular mechanisms by which CDC42 was responsible for the higher proliferation of HuH-7 cells mediated by HBx. We found that the expression level of CDC42 and its activity were significantly increased in HuH-7-HBx cells. The deficiency of CDC42 using the CRISPR/Cas9 system and inhibition by specific inhibitor CASIN led to the reduction of HBx-mediated proliferation. Furthermore, we observed that IQ Motif Containing GTPase Activating Protein 1 (IQGAP1), the downstream mediator of the CDC42 pathway, might be involved in the carcinogenesis induced by HBx. Therefore, the HBx/CDC42/IQGAP1 signaling pathway may potentially play an important role in HBx-mediated carcinogenesis.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. kukuxong.2008@163.com.|State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China. kukuxong.2008@163.com.
authors.forename: Yongru
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. qi840310@foxmail.com.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. nmluojj@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. 2012283060078@whu.edu.cn.|Key Laboratory of Combinatorial Biosynthesis and Drug Discoveryof Ministry of Education, School of Pharmaceutical Sciences, School of Basic Medical Science, Wuhan University, Wuhan 430071, China. 2012283060078@whu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. xieqi.tmmu@gmail.com.|Key Laboratory of Combinatorial Biosynthesis and Drug Discoveryof Ministry of Education, School of Pharmaceutical Sciences, School of Basic Medical Science, Wuhan University, Wuhan 430071, China. xieqi.tmmu@gmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. 18943956196@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. sunaisthefirst@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Su
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. powerweiwei@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China. ardsshi@gxu.edu.cn.
authors.forename: Deshun
authors.initials: D
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. xf_future_2005@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China. xiangpingli@163.com.
authors.forename: Xiangping
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China. xuping@mail.ncpsb.org.|Key Laboratory of Combinatorial Biosynthesis and Drug Discoveryof Ministry of Education, School of Pharmaceutical Sciences, School of Basic Medical Science, Wuhan University, Wuhan 430071, China. xuping@mail.ncpsb.org.|Graduate School, Anhui Medical University, Hefei 230032, China. xuping@mail.ncpsb.org.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins; D014945:Wound Healing; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D020543:Proteome; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D020764:cdc42 GTP-Binding Protein
keywords: CDC42; HBx; HuH-7 cell; hepatocellular carcinoma; quantitative proteomics