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

Biomed Pharmacother. 2013 Mar;67(2):97-102. doi: 10.1016/j.biopha.2012.11.008. Epub 2012 Dec 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / drug effects
  • 3' Untranslated Regions / genetics
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • MicroRNAs / genetics*
  • MutS Homolog 2 Protein / genetics*
  • MutS Homolog 2 Protein / metabolism
  • Up-Regulation / drug effects

Substances

  • 3' Untranslated Regions
  • MIRN21 microRNA, human
  • MicroRNAs
  • MSH2 protein, human
  • MutS Homolog 2 Protein
  • Cisplatin