title: Hepatitis B virus regulation of Raf1 promoter activity through activation of transcription factor AP-2α.
abstract: The X protein of hepatitis B virus (HBx) is one of the important factors in the development of hepatocellular carcinoma. Raf1 kinase is a central component of many signaling pathways that are involved in normal cell growth and oncogenic transformation. We previously demonstrated that hepatitis B virus regulates Raf1 expression in HepG2.2.15 cells by enhancing its promoter activity and that HBx and HBs might play an important role in this process. However, the underlying molecular mechanisms remain unclear. In this study, we show that nucleotides -209 to -133 of the Raf1 promoter sequence constitute the core region where hepatitis B virus is regulated. This regulation was found to require the involvement of cis-regulatory element AP-2α. We further demonstrated that AP-2α expression was higher in HepG2.2.15 cells (HBV-expressing cells) than in HepG2 cells in vitro. Silencing AP-2α expression by siRNA significantly inhibited the Raf1 promoter activity in HepG2.2.15 cells. These findings indicated that HBV regulates Raf1 promoter activity, possibly through AP-2α.
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Qu
authors.forename: Jianbo
authors.initials: J
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Dongdong
authors.initials: D
authors.lastname: Qin
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Sheng
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zou
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.forename: Ailong
authors.initials: A
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D011401:Promoter Regions, Genetic; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050656:Transcription Factor AP-2; D014764:Viral Proteins; D019908:Proto-Oncogene Proteins c-raf