miR-92a inhibits peritoneal dissemination of ovarian cancer cells by inhibiting integrin α5 expression

Am J Pathol. 2013 May;182(5):1876-89. doi: 10.1016/j.ajpath.2013.01.039. Epub 2013 Mar 15.


Ovarian cancer is characterized by widespread peritoneal dissemination and ascites and has a cure rate of only 30%. As has been previously reported, integrin α5 plays a key role in the peritoneal dissemination of ovarian cancer. Our aim was to identify a new miRNA that regulates integrin α5 expression and analyze the therapeutic potential of targeting this miRNA. By using an IHC analysis, we proved that high integrin α5 expression correlates with a poor prognosis in Japanese patients with International Federation of Gynecology and Obstetrics stage III ovarian cancer. Based on an miRNA algorithm search, we identified hsa-mir-92a (miR-92a) as a candidate. The level of miR-92a expression was significantly inversely correlated with ITGA5 expression in various cancer cells. Transfection of precursor miR-92a reduced integrin α5 expression in ovarian cancer cells, which was accompanied by the inhibition of cancer cell adhesion, invasion, and proliferation. miR-92a overexpression reduced the luciferase activity of the ITGA5 3'-untranslated region, suggesting that ITGA5 mRNA is a direct target of miR-92a. In in vivo ovarian cancer xenografts, the enforced expression of miR-92a in HeyA-8 cells suppressed peritoneal dissemination. Although we still have a long way to go before an effective and nontoxic miRNA-based cancer therapy can be introduced into the clinic, the inhibition of integrin α5 expression by targeting miR-92a needs to be explored further for future applications in ovarian cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Base Sequence
  • Biomarkers, Tumor / metabolism
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alpha5 / genetics
  • Integrin alpha5 / metabolism*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary*
  • Prognosis
  • Protein Binding / genetics
  • Xenograft Model Antitumor Assays
  • Young Adult


  • Biomarkers, Tumor
  • Integrin alpha5
  • MIRN92 microRNA, human
  • MicroRNAs