title: Cisplatin upregulates MSH2 expression by reducing miR-21 to inhibit A549 cell growth.
abstract: 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.
authors.affiliation: Key Laboratory of Tumour Molecular Biology in Binzhou Medical University, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, 264003, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yue
authors.forename: Ping-Yu
authors.initials: PY
authors.lastname: Wang
authors.forename: You-Jie
authors.initials: YJ
authors.lastname: Li
authors.forename: Jia-Xuan
authors.initials: JX
authors.lastname: Xin
authors.forename: Min
authors.initials: M
authors.lastname: Pang
authors.forename: Qing-Yin
authors.initials: QY
authors.lastname: Zheng
authors.forename: Shu-Yang
authors.initials: SY
authors.lastname: Xie
mesh_terms: D020413:3' Untranslated Regions / Q000187:drug effects / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D051718:MutS Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D002945:Cisplatin