HBX protein promotes LASP‐1 expression through activation of c‐Jun in human hepatoma cells

Autor: Yanbo Kou, Wenya Luo, Fanyun Kong, Xiao Wei, Xi Chen, Lei Hu, Hongjuan You, Renxian Tang, Kuiyang Zheng, Wei Hu, Kai Zhou, Xiao-Mei Liu
Rok vydání: 2018
Předmět:
Zdroj: Journal of Cellular Physiology. 233:7279-7291
ISSN: 1097-4652
0021-9541
DOI: 10.1002/jcp.26560
Popis: LIM and SH3 domain protein 1 (LASP-1) is known to participate in the progression of hepatocellular carcinoma (HCC). We previously showed that ectopic expression of hepatitis B virus (HBV) X protein (HBX) enhanced the expression of LASP-1, which promoted proliferation and migration of HCC cells. Here, we further demonstrated the molecular mechanism underlying upregulation of LASP-1, mediated by HBX, in HBV-infected HCC cells. Through a luciferase activity assay, we discovered that the LASP-1 promoter region regulated by HBX contained an AP-1 binding element in human hepatoma cells. Interestingly, c-Jun, one subunit of AP-1, was mainly responsible for activation, mediated by HBX, of the LASP-1 promoter. Furthermore, HBX was shown not only to interact with phosphorylated c-Jun in HCC cells but also to activate c-Jun by increasing the activation of PI3-K/JNK signaling. Chromatin immunoprecipitation (ChIP) assay demonstrated that HBX was capable of binding to the LASP-1 promoter with c-Jun. Further, the expression levels of HBX were shown to be significantly positively correlated with that of LASP-1 and phosphorylatedc-Jun in HBV-related HCC tissues by immunohistochemistry analysis. In addition, the N-terminus of HBX was found to be responsible for the activation of c-Jun, as well as the expression of LASP-1. Taken together, these results suggest that HBX contributes to LASP-1 expression via the activation of c-Jun to increase the promoter activity of LASP-1 in HBV-related HCC cells.
Databáze: OpenAIRE
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