HBX protein promotes LASP‐1 expression through activation of c‐Jun in human hepatoma cells. Issue 9 (30th March 2018)

• Record Type: Journal Article
• Authors: You, Hongjuan; Kong, Fanyun; Zhou, Kai; Wei, Xiao; Hu, Lei; Hu, Wei; Luo, Wenya; Kou, Yanbo; Liu, Xiaomei; Chen, Xi; Zheng, Kuiyang; Tang, Renxian
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 9(2018:Sep.)
• Page Start: 7279
• Page End: 7291
• Publication Date: 2018-03-30
• Subjects: c‐Jun -- HBX -- hepatocellular carcinoma -- LASP‐1; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26560
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : 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. Abstract : In this study, we found that the LASP‐1 promoter region regulated by HBX contained AP‐1 binding element in hepatoma cells, and c‐Jun, one subunit of AP‐1, was mainly responsible for the activation of LASP‐1 promoter mediated by HBX. Furthermore, HBX was identified to not only interact with phosphorylated c‐Jun but also activate c‐Jun via PI3‐K/JNK signaling in HCC cells.Taken together, our finding provides a novel insight into a better understanding of how HBX induce the expression of LASP‐1 to promote the development of HBV‐related HCC.