Cisplatin upregulates MSH2 expression by reducing miR-21 to inhibit A549 cell growth.
Cisplatin upregulates MSH2 expression by reducing miR-21 to inhibit A549 cell growth.
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DOI：
10.1016/j.biopha.2012.11.008
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Xie SY
中科院分区：
文献类型：
--
作者：
Zhang YX;Yue Z;Wang PY;Li YJ;Xin JX;Pang M;Zheng QY;Xie SY
miR-21可以作为致癌基因发挥作用。MSH 2参与DNA错配修复（DNA mismatch repair，MMR）系统，过表达MSH 2可诱导细胞凋亡。我们利用microRNA分析软件预测了miR-21靶向的MSH 2 -3′-非翻译区（3′-UTR）。为了进一步探讨miR-21和MSH 2在A549细胞中的作用，我们构建了含MSH 2 -3′-UTR的pcDNA-GFP-msh-UTR载体，将miR-21转染A549细胞，通过荧光显微镜和流式细胞仪检测GFP阳性细胞。Western blotting进一步证实miR-21可明显下调MSH 2的表达。此外，我们用顺铂处理A549细胞，发现顺铂在体外和体内都能抑制A549细胞的生长。我们还发现顺铂可以下调A549细胞中miR-21的表达，而增加MSH 2的表达。我们的研究结果表明，顺铂通过下调miR-21的表达，上调MSH 2的表达，从而抑制A549细胞的增殖，为药物设计和肿瘤治疗提供了新的基因靶点。
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.
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DOI：
10.1007/s00432-011-1140-8
发表时间：
2012-04-01
影响因子：
3.6
作者：
Cao, Zhang;Yoon, Jung Hwan;Park, Won Sang
通讯作者：
Park, Won Sang
影响因子：
4.8
作者：
Meyers, M;Wagner, MW;Boothman, DA
通讯作者：
Boothman, DA
通过抗 miR-150 载体消退 A549 肺癌肿瘤。
影响因子：
4.2
作者：
Li, You-Jie;Zhang, Yan-Xa;Xie, Shu-Yang
通讯作者：
Xie, Shu-Yang
影响因子：
8
作者：
Si, M.-L.;Zhu, S.;Mo, Y.-Y.
通讯作者：
Mo, Y.-Y.
影响因子：
120.7
作者：
Schetter, Aaron J.;Leung, Suet Yi;Harris, Curtis C.
通讯作者：
Harris, Curtis C.