Involvement of microRNA-93, a New Regulator of PTEN/Akt Signaling Pathway, in Regulation of Chemotherapeutic Drug Cisplatin Chemosensitivity in Ovarian Cancer Cells

FEBS Lett. 2012 May 7;586(9):1279-86. doi: 10.1016/j.febslet.2012.03.006. Epub 2012 Mar 27.

Abstract

The mechanisms underlying ovarian cancer cell resistance to cisplatin (CDDP) are not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis and drug resistance. In this paper, we utilized microRNA array and real-time PCR to show that miR-93 is significantly up-regulated in cisplatin-resistant ovarian cancer cells. In vitro assays show that over-expression and knock-down of miR-93 regulate apoptotic activity, and thereby cisplatin chemosensitivity, in ovarian cells. Furthermore, we found that miR-93 can directly target PTEN, and participates in the regulation of the AKT signaling pathway. MiR-93 inversely correlates with PTEN expression in CDDP-resistant and sensitive human ovarian cancer tissues. These results may have implications for therapeutic strategies aiming to overcome ovarian cancer cell resistance to cisplatin.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Silencing
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Ovarian Neoplasms / pathology*
  • PTEN Phosphohydrolase / deficiency
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism*
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / genetics
  • Signal Transduction / genetics*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Antineoplastic Agents
  • MIRN93 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Cisplatin