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Hepatitis B virus regulation of Raf1 promoter activity through activation of transcription factor AP-2α

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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.

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Acknowledgment

This work was supported by Nature Science Foundation of China (30771924) and Natural Science Foundation Project of CQ CSTC (2010BB5359). We thank Prof. Limin Chen of the Toronto General Research Institute, University of Toronto, for critical reading of the manuscript.

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Authors and Affiliations

  1. Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China

    Jialin Qu, Ke Chen, Dongdong Qin, Kai Li, Yanrui Sheng, Chengcheng Zou, Sen Wang, Ailong Huang & Hua Tang

  2. Department of Forensic Medicine, Chongqing Medical University, Chongqing, 400016, China

    Jianbo Li

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  1. Jialin Qu
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  2. Jianbo Li
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Correspondence to Hua Tang.

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J. Qu and J. Li contributed equally to this work.

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Qu, J., Li, J., Chen, K. et al. Hepatitis B virus regulation of Raf1 promoter activity through activation of transcription factor AP-2α. Arch Virol 158, 887–894 (2013). https://doi.org/10.1007/s00705-012-1561-y

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