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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6952


    Title: Histone deacetylase inhibitor suberoylanilide hydroxamic acid suppresses the pro-oncogenic effects induced by hepatitis B virus pre-S2 mutant oncoprotein and represents a potential chemopreventive agent in high-risk chronic HBV patients
    Authors: Hsieh, YH;Su, IJ;Yen, CJ;Tsai, TF;Tsai, HW;Tsai, HN;Huang, YJ;Chen, YY;Ai, YL;Kao, LY;Hsieh, WC;Wu, HC;Huang, W
    Contributors: Division of Infectious Diseases
    Abstract: Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S2 mutant large HBV surface antigen (LHBS) in type II ground glass hepatocytes (GGHs) has been recognized as an emerging viral oncoprotein; it directly interacts with the c-Jun activation domain-binding protein 1 (JAB1) and subsequently causes hyperphosphorylation of the tumor suppressor retinoblastoma and, consequently, leads to disturbed cell cycle progression. The interaction of the pre-S2 mutant LHBS with JAB1 could provide a potential target for chemoprevention. In this study, we found that the preneoplastic type II GGHs showed a significant decrease of the cyclin-dependent kinase inhibitor p27Kip1, which serves as a marker for pre-S2 mutant-JAB1 complex formation. The histone deacetylase (HDAC) inhibitor SAHA elevated expression of the tumor suppressor thioredoxin-binding protein 2 (TBP2), which subsequently enhanced the JAB1-TBP2 interaction and abolished the pre-S2 mutant LHBS-induced degradation of p27Kip1, which, in turn, recovered the normal cell cycle checkpoint. The pre-S2 mutant LHBS-induced pro-oncogenic effects: increased cell proliferation, nuclear/cytoplasmic ratio and PCNA expression, were all greatly ameliorated after SAHA treatments, which suggested SAHA as a promising chemopreventive agent for the pre-S2 mutant oncoprotein-induced HCC. In conclusion, this study provides the mechanism of HDAC inhibitor in preventing the pre-S2 mutant-induced oncogenic phenotype. The HDAC inhibitor SAHA is therefore a potential chemopreventive agent for high-risk chronic HBV patients who may develop HCC.
    Date: 2013-02
    Relation: Carcinogenesis. 2013 Feb;34(2):475-485.
    Link to: http://dx.doi.org/10.1093/carcin/bgs365
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0143-3334&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000315627900028
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84873562300
    Appears in Collections:[蘇益仁(2002-2015)] 期刊論文

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