MicroRNA-509-3p increases the sensitivity of epithelial ovarian cancer cells to cisplatin-induced apoptosis

Pharmacogenomics. 2016 Feb;17(3):187-97. doi: 10.2217/pgs.15.166. Epub 2016 Jan 20.

Abstract

Aims: XIAP is upregulated in chemoresistant epithelial ovarian cancer (EOC). However, the molecular mechanism of this dysregulation remains unclear.

Materials & methods: The regulation of XIAP by miR-509-3p was investigated by luciferase reporter assay, real-time PCR and immunobloting, and the roles of miR-509-3p in cellular proliferation and apoptosis were accessed through MTT and DAPI assays.

Results: miR-509-3p, a downregulated miRNA in chemoresistant EOC, can directly target the XIAP via its 3'UTR. Overexpression of miR-509-3p can not only downregulate the expression of XIAP in ovarian cancer cells but also inhibit the proliferation of EOC cells and increase their sensitivity to cisplatin-induced apoptosis.

Conclusions: Our data suggest that restoring certain dysregulated miRNAs to their normal levels could increase the therapeutic effects of anticancer drugs.

Keywords: X-linked inhibitor of apoptosis; cell apoptosis; cell proliferation; microRNA-509–3p; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology*
  • Female
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Luciferases, Renilla / genetics
  • Luciferases, Renilla / metabolism
  • MicroRNAs / metabolism*
  • Ovarian Neoplasms
  • X-Linked Inhibitor of Apoptosis Protein / genetics

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • MIRN509 microRNA, human
  • MicroRNAs
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Luciferases, Renilla
  • Cisplatin