Hepatitis B virus X (HBX) protein upregulates β-catenin in a human hepatic cell line by sequestering SIRT1 deacetylase

  • Authors:
    • Ratakorn Srisuttee
    • Sang Seok Koh
    • Su Jin Kim
    • Waraporn Malilas
    • Wassamon Boonying
    • Il-Rae Cho
    • Byung Hak Jhun
    • Masafumi Ito
    • Yoshiyuki Horio
    • Edward Seto
    • Sangtaek Oh
    • Young-Hwa Chung
  • View Affiliations

  • Published online on: May 4, 2012     https://doi.org/10.3892/or.2012.1798
  • Pages: 276-282
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Abstract

Hepatitis B virus X (HBX) protein has been reported to induce upregulation of β-catenin, a known proto-oncogene, in p53-knockout and p53-mutant hepatic cell lines both in a GSK-3β-dependent manner and via interaction with adenomatous polyposis coli, which results in protection from β-catenin degradation. In this study, we describe a novel mechanism for HBX-mediated upregulation of β-catenin. We observed that HBX interacts with SIRT1, a class III histone deacetylase. Furthermore, the presence of HBX attenuated the interaction between SIRT1 and β-catenin, leading to protection of β-catenin from the inhibitory action of SIRT1. Reduction of SIRT1 with siRNA or suppression of SIRT1 activity with nicotinamide upregulated β-catenin protein levels. In contrast, enhancement of SIRT1 activity with resveratrol reduced β-catenin protein levels. Furthermore, in Hep3B cells stably expressing HBX, overexpression of SIRT1 or treatment with resveratrol enhanced sensitivity to doxorubicin-induced apoptosis, indicating that upregulation of SIRT1 could be a therapeutic strategy for HBV-related hepatocellular carcinoma. Based on these results, we propose that HBX upregulates β-catenin by sequestering SIRT1, which leads to anticancer drug treatment resistance.

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July 2012
Volume 28 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Srisuttee, R., Koh, S.S., Kim, S.J., Malilas, W., Boonying, W., Cho, I. ... Chung, Y. (2012). Hepatitis B virus X (HBX) protein upregulates β-catenin in a human hepatic cell line by sequestering SIRT1 deacetylase. Oncology Reports, 28, 276-282. https://doi.org/10.3892/or.2012.1798
MLA
Srisuttee, R., Koh, S. S., Kim, S. J., Malilas, W., Boonying, W., Cho, I., Jhun, B. H., Ito, M., Horio, Y., Seto, E., Oh, S., Chung, Y."Hepatitis B virus X (HBX) protein upregulates β-catenin in a human hepatic cell line by sequestering SIRT1 deacetylase". Oncology Reports 28.1 (2012): 276-282.
Chicago
Srisuttee, R., Koh, S. S., Kim, S. J., Malilas, W., Boonying, W., Cho, I., Jhun, B. H., Ito, M., Horio, Y., Seto, E., Oh, S., Chung, Y."Hepatitis B virus X (HBX) protein upregulates β-catenin in a human hepatic cell line by sequestering SIRT1 deacetylase". Oncology Reports 28, no. 1 (2012): 276-282. https://doi.org/10.3892/or.2012.1798