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

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Title
Hepatitis B virus X (HBX) protein upregulates β-catenin in a human hepatic cell line by sequestering SIRT1 deacetylase
Author(s)
R Srisuttee; Sang Seok Koh; Su Jin Kim; W Malilas; W Boonying; I R Cho; B H Jhun; M Ito; Y Horio; D Seto; S Oh; Y H Chung
Bibliographic Citation
Oncology Reports, vol. 28, no. 1, pp. 276-282
Publication Year
2012
Abstract
Hepatitis B virus X (HBX) protein has been reported to induce upregulation of β-catenin, a known protooncogene, 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 SIRT1activity with resveratrol reduced β-catenin protein levels. Furthermore, in Hep3B cells stably expressing HBX, overexpression of SIRT1or 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.
Keyword
β-cateninApoptosisDoxorubicinHepatitis B virus XSIRT1
ISSN
1021-335X
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/or.2012.1798
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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