國家衛生研究院 NHRI:Item 3990099045/8191
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    題名: Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis
    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: Autophagy and microRNA (miRNA) are important regulators during cancer cell tumorigenesis. Impaired autophagy and high expression of the oncogenic microRNA MIR224 are prevalent in hepatocellular carcinoma (HCC); however, the relationship between the 2 phenomena remains elusive. In this study, we are the first to reveal that autophagy selectively regulates MIR224 expression through an autophagosome-mediated degradation system. Based on this finding, we further demonstrated that in hepatitis B virus (HBV)-related HCC, aberrant autophagy (low autophagic activity) results in accumulation of MIR224 and decreased expression of the target gene Smad4, which leads to increased cell migration and tumor formation. Preferential recruitment of MIR224 into the autophagosome was clearly demonstrated by a) miRNA in situ hybridization under confocal microscopy, and b) immunogold labeling of MIR224 under electron microscopy compared with a ubiquitously expressed microRNA MIRlet7e/let-7. Furthermore, we found that off-label use of amiodarone, an antiarrhythmic agent, effectively suppressed HCC tumorigenesis through autophagy-mediated MIR224 degradation both in vitro and in vivo. In summary, we identified amiodarone as a new autophagy inducer, which may provide an alternative approach in HCC therapy through a novel tumor suppression mechanism.
    日期: 2014-09
    關聯: Autophagy. 2014 Sep;10(9):1687-1689.
    Link to: https://www.landesbioscience.com/journals/autophagy/article/29959/?nocache=1148912644
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1554-8627&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000341647200019
    顯示於類別:[蘇益仁(2002-2015)] 期刊論文

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