Literature Information
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PubMed PMID
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30070724
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Published year
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2019 |
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Journal
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Hepatology (Baltimore, Md.) |
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Title
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Androgen Receptor Enhances Hepatic Telomerase Reverse Transcriptase Gene Transcription After Hepatitis B Virus Integration or Point Mutation in Promoter Region. |
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Author
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Li CL,Li CY,Lin YY,Ho MC,Chen DS,Chen PJ,Yeh SH |
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Evidence
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The majority of such HCC cases contain integrated HBV, and some hotspot integrations, such as those in the telomerase reverse transcriptase gene (TERT) promoter, activate gene expression to drive carcinogenesis. As the HBV genome contains both androgen-responsive and estrogen-responsive motifs, we hypothesized that the integrated HBV DNA renders a similar regulation for downstream gene expression and thus contributes to male susceptibility to HCC. To test this hypothesis, the HBV integration sites and the common mutations in the TERT promoter and tumor protein P53 (TP53) coding region were analyzed in 101 HBV-related HCC cases using a capture-next-generation sequencing platform. The results showed that both HBV integration and -124G>A mutation in the TERT promoter region, occurring in a mutually exclusive manner, were more frequent in male than in female patients with HCC (integration: 22/58 male patients with HCC, 6/36 female patients with HCC, P = 0. HBV integration in the TERT promoter rendered the TERT transcription responsive to sex hormones, with enhancement by androgen receptor (AR) but suppression by estrogen receptor, both of which were dependent on hepatocyte nuclear factor 4 alpha. Conclusion: TERT elevation by AR through integrated HBV and point mutation at the TERT promoter region was identified as a mechanism for the male dominance of HBV-related HCCs; telomerase and AR thus may be targets for intervention of HCC.
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HBV VIS Detail Information