MicroRNA200a enhances antitumor effects in combination with doxorubicin in hepatocellular carcinoma
MicroRNA200a enhances antitumor effects in combination with doxorubicin in hepatocellular carcinoma
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DOI：
10.1016/j.tranon.2020.100805
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发表时间：
2020-10-01
影响因子：
5
通讯作者：
Geller, David A.
中科院分区：
文献类型：
--
作者：
Cui, Xiao;Zhou, Dachen;Geller, David A.
肝细胞癌（HCC）通常用阿霉素治疗。MicroRNA已被证明在癌症中具有重要的调节作用，并作为化学抗性的靶标。在这项研究中，我们研究了特异性microRNA-200 a（miR-200 a）对肝癌细胞生长的影响以及阿霉素介导的细胞毒性的影响。我们的研究结果显示miR-200 a在人HCC和HCC肿瘤细胞系中下调。增加miR-200 a表达抑制HCC生长，并与阿霉素的抗肿瘤作用协同。抑制内源性miR-200 a促进肿瘤生长和化疗耐药性。增加miR-200 a表达抑制肿瘤代谢（ATP产生、线粒体呼吸、糖酵解），而抑制内源性miR-200 a逆转了这些作用。MiR-200 a表达也增加了自噬，并与阿霉素介导的细胞毒性协同作用。这项研究确定了miR-200 a在增强阿霉素介导的HCC治疗效果中的新作用。
Hepatocellular carcinoma (HCC) is often treated with doxorubicin. MicroRNAs have been shown to have important regulatory roles in cancer and serve as a target in chemoresistance. In this study, we investigated the effects of specific microRNA-200a (miR-200a) on HCC tumor cell growth and effect of doxorubicin-mediated cytotoxicity. Our results show miR-200a is downregulated in human HCC and HCC tumor cell lines. Increasing miR-200a expression inhibited HCC growth and synergized with the antitumor effects of doxorubicin. Inhibiting endogenous miR-200a promoted tumor growth and chemotherapeutic resistance. Increasing miR-200a expression inhibited tumor metabolism (ATP production, mitochondrial respiration, glycolysis), while inhibition of endogenous miR-200a reversed these effects. MiR-200a expression also increased autophagy and synergized with doxorubicin-mediated cytotoxicity. This study identifies a novel role of miR-200a in potentiating doxorubicin-mediated therapeutic effects in HCC.