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miR-30a Regulates the Expression of CAGE and p53 and Regulates the Response to Anti-Cancer Drugs

  • Park, Deokbum (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Kim, Hyuna (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Kim, Youngmi (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Jeoung, Dooil (Department of Biochemistry, College of Natural Sciences, Kangwon National University)
  • Received : 2015.09.15
  • Accepted : 2016.01.12
  • Published : 2016.04.30

Abstract

We have previously reported the role of miR-217 in anti-cancer drug-resistance. miRNA array and miRNA hybridization analysis predicted miR-30a-3p as a target of miR-217. miR-30a-3p and miR-217 formed a negative feedback loop and regulated the expression of each other. Ago1 immunoprecipitation and co-localization analysis revealed a possible interaction between miR-30a-3p and miR-217. miR-30a-3p conferred resistance to anti-cancer drugs and enhanced the invasion, migration, angiogenic, tumorigenic, and metastatic potential of cancer cells in CAGE-dependent manner. CAGE increased the expression of miR-30a-3p by binding to the promoter sequences of miR-30a-3p, suggesting a positive feedback loop between CAGE and miR-30a-3p. miR-30a-3p decreased the expression of p53, which showed the binding to the promoter sequences of miR-30a-3p and CAGE in anti-cancer drug-sensitive cancer cells. Luciferase activity assays showed that p53 serves as a target of miR-30a. Thus, the miR-30a-3p-CAGE-p53 feedback loop serves as a target for overcoming resistance to anti-cancer drugs.

Keywords

anti-cancer drug-resistance;CAGE;feedback loop;miR-30a;p53

Acknowledgement

Supported by : National Research Foundation, Ministry for Health and Welfare

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