Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition
Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition
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DOI：
10.7150/ijbs.32460
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发表时间：
2020-01-01
影响因子：
9.2
通讯作者：
Wang, Xiang
中科院分区：
文献类型：
--
作者：
Bao, Ying;Zhang, Yibo;Wang, Xiang
我们研究了microRNA（miR）-9在调节肝细胞癌（HCC）细胞化疗耐药性中的作用。miR-9在HCC细胞系中过表达或被敲低。检测细胞活力、细胞增殖、EIF 5A 2和上皮-间质转化（EMT）相关蛋白的表达。过表达miR-9的HCC细胞对顺铂更敏感; miR-9敲低产生相反的结果。体内裸鼠HCC异种移植瘤产生相同的结果。EIF 5A 2是miR-9的潜在靶点，miR-9在mRNA和蛋白水平调控EIF 5A 2的表达。EIF 5A 2敲低逆转了miR-9抑制介导的顺铂耐药性。改变miR-9和EIF 5A 2的表达改变了E-钙粘蛋白和波形蛋白的表达。此外，EIF 5A 2介导miR-9 EMT通路调节，表明miR-9可通过靶向EIF 5A 2并抑制EMT通路来增强顺铂敏感性。靶向miR-9可能有助于克服HCC的耐药性。
We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial-mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition-mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC.