國家衛生研究院 NHRI:Item 3990099045/7458
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    題名: Autophagy suppresses tumorigenesis of hepatitis B virus-associated hepatocellular carcinoma through degradation of microRNA-224
    作者: Lan, SH;Wu, SY;Zuchini, R;Lin, XZ;Su, IJ;Tsai, TF;Lin, YJ;Wu, CT;Liu, HS
    貢獻者: Division of Infectious Diseases
    摘要: In hepatocelluar carcinoma (HCC), dysregulated expression of microRNA-224 (miR-224) and impaired autophagy have been reported separately. However, the relationship between them has not been explored. In this study, we determine that autophagy is down-regulated and inversely correlated with miR-224 expression in hepatitis B virus (HBV)-associated HCC patient specimens. These results were confirmed in liver tumors of HBV X gene transgenic mice. Furthermore, miR-224 was preferentially recruited and degraded during autophagic progression demonstrated by real-time PCR and miRNA in situ hybridization electron microscopy after extraction of autophagosomes. Our in vitro study demonstrated that miR-224 played an oncogenic role in hepatoma cell migration and tumor formation through silencing its target gene Smad4. In HCC patients, the expression of low-Atg5, high-miR-224 and low-Smad4 shows significant correlation with HBV infection and poor overall survival rate. Autophagy mediated miR-224 degradation and liver tumor suppression were further confirmed by the autophagy inducer amiodarone and miR-224 antagonist using an orthotopic SD rat model. Conclusion: we reveal a non-canonical pathway which links autophagy, miR-224, Smad4 and HBV-associated HCC. Our novel findings open a new avenue for the treatment of HCC. (Hepatology 2013;).
    日期: 2013-08
    關聯: Hepatology. 2014 Feb;59(2):505-517.
    Link to: http://dx.doi.org/10.1002/hep.26659
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0270-9139&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000330310300018
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84893081987
    顯示於類別:[蘇益仁(2002-2015)] 期刊論文

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