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HBX protein promotes LASP‐1 expression through activation of c‐Jun in human hepatoma cells
Author(s) -
You Hongjuan,
Kong Fanyun,
Zhou Kai,
Wei Xiao,
Hu Lei,
Hu Wei,
Luo Wenya,
Kou Yanbo,
Liu Xiaomei,
Chen Xi,
Zheng Kuiyang,
Tang Renxian
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26560
Subject(s) - hbx , c jun , chromatin immunoprecipitation , ectopic expression , chemistry , microbiology and biotechnology , downregulation and upregulation , cancer research , promoter , luciferase , biology , transfection , gene expression , gene , transcription factor , biochemistry
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.