Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Department of Hepatobiliary and Pancreatic Surgery, Lishui Hospital, Zhejiang University School of Medicine, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, P.R. China.
J Cell Mol Med. 2019 Nov;23(11):7190-7199. doi: 10.1111/jcmm.14197. Epub 2019 Feb 23.
Drug resistance occurs commonly in cancers, especially in hepatocellular carcinoma (HCC). Accumulating evidence has demonstrated that microRNAs (miRNAs) play a vital role in tumour chemoresistance. However, little is known about the role of miR-383 in HCC chemoresistance. In the present study, RT-PCR and western blotting were used to identify the expression profile of miR-383 and eukaryotic translation initiation factor 5A2 (EIF5A2). The bioinformatics website Targetscan was used to predict the target genes of miR-383. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and potential mechanism of the miR-383/EIF5A2 axis in chemoresistance of HCC cells. The expression level of miR-383 correlated negatively with doxorubicin (Dox) sensitivity. Overexpression of miR-383 promoted HCC cells to undergo Dox-induced cytotoxicity and apoptosis, whereas miR-383 knockdown had the opposite effects. EIF5A2 was predicted as a target gene of miR-383. EIF5A2 knockdown sensitized HCC cells to Dox. Moreover, miR-383 inhibition-mediated HCC Dox resistance could be reversed by silencing EIF5A2. Finally, we demonstrated that miR-383 inhibition could enhance Dox sensitivity by targeting EIF5A2 in vivo. The results indicated that miR-383 inhibited Dox resistance in HCC cells by targeting EIF5A2. Targeting the miR-383/EIF5A2 axis might help to alleviate the chemoresistance of HCC cells.
耐药性在癌症中很常见，尤其是在肝细胞癌 (HCC) 中。越来越多的证据表明，microRNAs (miRNAs) 在肿瘤化疗耐药中发挥着重要作用。然而，miR-383 在 HCC 化疗耐药中的作用知之甚少。在本研究中，使用 RT-PCR 和 Western blot 鉴定了 miR-383 和真核翻译起始因子 5A2 (EIF5A2) 的表达谱。使用生物信息学网站 Targetscan 预测 miR-383 的靶基因。进行体外和体内的失活和功能获得研究，以揭示 miR-383/EIF5A2 轴在 HCC 细胞化疗耐药中的作用和潜在机制。miR-383 的表达水平与阿霉素 (Dox) 敏感性呈负相关。miR-383 的过表达促进 HCC 细胞发生 Dox 诱导的细胞毒性和细胞凋亡，而 miR-383 的下调则产生相反的效果。EIF5A2 被预测为 miR-383 的靶基因。EIF5A2 的下调使 HCC 细胞对 Dox 敏感。此外，沉默 EIF5A2 可以逆转 miR-383 抑制介导的 HCC Dox 耐药性。最后，我们证明 miR-383 通过靶向 EIF5A2 在体内增强了 Dox 的敏感性。结果表明，miR-383 通过靶向 EIF5A2 抑制 HCC 细胞的 Dox 耐药性。靶向 miR-383/EIF5A2 轴可能有助于减轻 HCC 细胞的化疗耐药性。
