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Hepatitis B Virus X Protein Stimulates Proliferation, Wound Closure and Inhibits Apoptosis of HuH-7 Cells via CDC42.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2017 Mar 08; Vol. 18 (3). Date of Electronic Publication: 2017 Mar 08. - Publication Year :
- 2017
-
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.
- Subjects :
- Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular virology
Cell Line, Tumor
Cell Proliferation
Gene Expression
Gene Knockout Techniques
Humans
Liver Neoplasms genetics
Liver Neoplasms metabolism
Liver Neoplasms virology
Proteome
Proteomics methods
Viral Regulatory and Accessory Proteins
cdc42 GTP-Binding Protein genetics
cdc42 GTP-Binding Protein metabolism
Apoptosis
Trans-Activators metabolism
Wound Healing
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 18
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 28282856
- Full Text :
- https://doi.org/10.3390/ijms18030586