國家衛生研究院 NHRI:Item 3990099045/14178
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    题名: Transcriptional suppression of Dicer by HOXB-AS3/EZH2 complex dictates sorafenib resistance and cancer stemness
    作者: Tseng, CF;Chen, LT;Wang, HD;Liu, YH;Shiah, SG
    贡献者: National Institute of Cancer Research
    摘要: Sorafenib is a multikinase inhibitor for the standard treatment of advanced liver cancer patients. However, acquired resistance to sorafenib is responsible for a poor prognosis. Therefore, uncovering the molecular mechanisms underlying sorafenib sensitization can provide biomarkers for sorafenib treatment and improve sorafenib activity in a precise medication. Here, we report that epigenetic suppression of Dicer by the HOXB-AS3/EZH2 complex is responsible for sorafenib resistance. We observed that Dicer expression is inversely correlated with EZH2 levels, HOXB-AS3 expression, sorafenib resistance, and cancer stem cell properties in liver cancer patients. Furthermore, ectopic expression of Dicer induced liver cancer cells resensitization to sorafenib. Mechanistically, we found HOXB-AS3 physically interacts with EZH2 and recruits EZH2 to the Dicer promoter, resulting in epigenetic suppression of Dicer expression. These findings reveal that HOXB-AS3/EZH2 complex-mediated Dicer suppression plays an important role in sorafenib resistance and cancer stemness and provide potential therapeutic strategies for diagnosing and treating liver cancer patients.
    日期: 2022-05
    關聯: Cancer Science. 2022 May;113(5):1601-1612.
    Link to: http://dx.doi.org/10.1111/cas.15319
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1347-9032&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000768627500001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85126239754
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