Downregulation of miR-130a contributes to cisplatin resistance in ovarian cancer cells by targeting X-linked inhibitor of apoptosis (XIAP) directly

Acta Biochim Biophys Sin (Shanghai). 2013 Dec;45(12):995-1001. doi: 10.1093/abbs/gmt113. Epub 2013 Oct 20.

Abstract

MicroRNAs (miRNAs) are short, highly conserved small non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes. Recent studies have shown that dysregulation of miRNAs might modulate the resistance of cancer cells to chemotherapeutic agents. To investigate the possible role of miR-130a in the development of cisplatin resistance in human ovarian cancer cell line A2780, we evaluated the expression of microRNA-130a (miR-130a) in the cells by the quantitative real-time reverse transcription-polymerase chain reaction. The results showed that miR-130a was significantly down-regulated in cisplatin-resistant ovarian cancer cells. MTT assay and flow cytometry (FCM) results showed that over-expression of miR-130a regulated apoptotic activity, and thereby cisplatin chemosensitivity, in ovarian cancer cells. Furthermore, we found that miR-130a can directly target XIAP, and participate in the regulation of apoptosis. The up-regulation of miR-130a led to a significant decrease in the XIAP mRNA levels and protein levels. XIAP plays an important role in cisplatin resistance in ovarian cancer cell line A2780. Our findings suggested that miR-130a could play a role in the development of cisplatin resistance in ovarian cancer cell line A2780, at least in part by modulation of apoptosis via targeting XIAP.

Keywords: XIAP; cisplatin resistance; miR-130a; ovarian cancer.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cisplatin / pharmacology*
  • Down-Regulation*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • X-Linked Inhibitor of Apoptosis Protein / genetics*
  • X-Linked Inhibitor of Apoptosis Protein / metabolism

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • MIRN130 microRNA, human
  • MicroRNAs
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Luciferases
  • Cisplatin