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Hepatitis B virus X protein upregulates transcriptional activation of human telomerase reverse transcriptase

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Abstract

It is well known that telomerase activation and virus infection are strongly associated with human hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) plays an important role in HCC pathogenesis. However, the mechanisms of HBx on telomerase activity are not well understood. To determine the potential roles of HBx in telomerase activity, both transfection and antisense assay were designed to examine the effects of HBx on telomerase in this report. Results showed that HBX gene increased telomerase activity and human telomerase reverse transcriptase (hTERT) expression in HBx-transfected cells and HBx-positive HCC samples. Co-transfection and luciferase reporter assay showed that HBx could stimulate hTERT promoter in a dose-dependent manner in different cells. Truncated and mutant reporter assays revealed that Sp1 binding sites mapped at −132 to +5 nt in hTERT promote were important for HBx-mediated upregulation of hTERT. Western blot did not show any change of Sp1 expression in HBx-transfected cells, but EMSA showed evidence of that HBx increased binding of Sp1 to its target DNA. These results provide new insights into the role of HBx in liver carcinogenesis.

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Acknowledgments

We thank the Institute of Genetics, Shandong University School of Medicine for assistance with the Luciferase assays. This work was supported by grants from the National Nature Science Foundation of China (No. 30972753 and No. 30670966), the National Basic Research Program (973), No. 2009CB521900, Shandong Provincial Nature Science Foundation for Distinguished Young Scholars (JQ200907), and Independent Innovation Foundation of Shandong University.

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Authors and Affiliations

  1. The Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, 4# Wenhua Xi Road, 250012, Jinan, People’s Republic of China

    Chunhong Ma

  2. Institute of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, 250012, Jinan, People’s Republic of China

    Hua Liu, Wei Shi, Fang Luan, Wensheng Sun & Chunhong Ma

  3. Department of Surgery, Shandong Provincial Hospital, 324# Jingwu Road, 250021, Jinan, Shandong, People’s Republic of China

    Shifeng Xu, Fenghui Yang & Jun Liu

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  1. Hua Liu
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  2. Wei Shi
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  3. Fang Luan
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  7. Jun Liu
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Correspondence to Jun Liu or Chunhong Ma.

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Liu, H., Shi, W., Luan, F. et al. Hepatitis B virus X protein upregulates transcriptional activation of human telomerase reverse transcriptase. Virus Genes 40, 174–182 (2010). https://doi.org/10.1007/s11262-009-0441-3

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  • DOI: https://doi.org/10.1007/s11262-009-0441-3

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