國家衛生研究院 NHRI:Item 3990099045/11042
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    题名: Epigenetic regulation of LDHA dictates the gemcitabine resistance in pancreatic cancer
    作者: Chiu, CF
    贡献者: National Institute of Cancer Research
    摘要: Acquisition of resistance to gemcitabine in pancreatic cancer remains a major challenge. Here, we investigated the metabolite profiles by liquid chromatography-mass spectrometry between gemcitabine-resistant and parental cancer cells, and found that lactic acid amount and lactate dehydrogenase activity were increased in gemcitabine-resistant cancer cells. We observed the elevated lactate dehydrogenase A (LDHA) expression significantly correlated with recurrent pancreatic cancer patients following gemcitabine treatment and with cancer stem cell (CSC) properties. By approaching the comparative array-based microRNA expression and transcription analysis, we further identified that FOXO3a-induced miR-4259 directly targeted the 3'untranslated region of LDHA and reduced LDHA expression, leading to decreased gemcitabine resistance and CSC phenotypes. Our findings suggest that LDHA might serve as a therapeutic target for pancreatic cancer, particularly gemcitabine-resistant pancreatic cancer, and may provide evidence of an underlying epigenetic regulation of LDHA by FOXO3a/miR-4259, which appears to be involved in cancer stemness and the chemoresistance of pancreatic cancer.
    日期: 2018-01
    關聯: Cancer Science. 2018 Jan;109(Suppl. 1):1146.
    Link to: http://dx.doi.org/10.1111/cas.13499
    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:000422694006340
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