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

Mol Cells. 2016 Apr 30;39(4):299-309. doi: 10.14348/molcells.2016.2242. Epub 2016 Feb 25.

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Melanoma / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Neoplasms, Experimental
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • MIRN217 microRNA, human
  • MIRN30b microRNA, human
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • DDX53 protein, human
  • DEAD-box RNA Helicases