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Cisplatin upregulates MSH2 expression by reducing miR-21 to inhibit A549 cell growth

机译:顺铂通过减少miR-21抑制A549细胞生长来上调MSH2表达

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摘要

miR-21 can act as an oncogene. MSH2 has been reported that it involved in the DNA mismatch repair (MMR) system and overexpression of MSH2 can induce cell apoptosis. We predicted that MSH2-3'-untranslated region (3'-UTR) was targeted by miR-21 using microRNA analysis softwares. To further explore the roles of miR-21 and MSH2 in A549 cells, we constructed pcDNA-GFP-msh-UTR vector (including MSH2-3'-UTR) to transfect A549 cells with miR-21, GFP positive cells were estimated under a fluorescence microscopy and by flow cytometry. We found miR-21 could obviously downregulate the expression of MSH2, which was further proved by western blotting. Moreover, we treated A549 cells with cisplatin and found that cisplatin could inhibit A549 cell growth in vitro and in vivo. We also found that cisplatin could downregulate miR-21 expression, while increase MSH2 expression in A549 cells. Our results demonstrated that cisplatin could upregulate the expression of MSH2 through downregulating miR-21 to inhibit A549 cell proliferation, which provides new gene targets for drug design or cancer therary.
机译:miR-21可以作为癌基因。据报道,MSH2参与DNA错配修复(MMR)系统,而MSH2的过表达可诱导细胞凋亡。我们预测,使用microRNA分析软件,miR-21可靶向MSH2-3'非翻译区(3'-UTR)。为了进一步探讨miR-21和MSH2在A549细胞中的作用,我们构建了pcDNA-GFP-msh-UTR载体(包括MSH2-3'-UTR)以miR-21转染A549细胞,在荧光显微镜和流式细胞仪。我们发现miR-21可以明显下调MSH2的表达,这已通过蛋白质印迹进一步证实。此外,我们用顺铂处理A549细胞,发现顺铂可在体外和体内抑制A549细胞的生长。我们还发现顺铂可以下调miR-21表达,同时增加A549细胞中的MSH2表达。我们的结果表明,顺铂可通过下调miR-21来抑制A549细胞增殖,从而上调MSH2的表达,这为药物设计或癌症治疗提供了新的基因靶标。

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