miR-9 functions as a tumor suppressor in ovarian serous carcinoma by targeting TLN1

Int J Mol Med. 2013 Aug;32(2):381-8. doi: 10.3892/ijmm.2013.1400. Epub 2013 May 30.

Abstract

microRNAs (miRNAs) are important regulators of gene expression during tumorigenesis. The downregulation of microRNA-9 (miR-9) has been reported in ovarian serous carcinoma (OSC), indicating a role for miR-9 in this type of cancer. In this study, we investigated the biological significance of miR-9 in OSC in vitro. Using 3 OSC cell lines, SKOV3, CAOV3 and OVCAR3, which underexpresss miR-9, we demonstrate that the exogenous miR-9 transfection inhibits OSC cell proliferation, migration and invasion. In addition, we demonstrate that the focal adhesion protein, talin 1 (TLN1), whose expression has been associated with OSC development and progression to metastasis, is a direct target of miR-9. TLN1 knockdown mimicked the effects of miR-9 overexpression. Moreover, the activation of the TLN1-modulated FAK/AKT pathway was inhibited by the increased miR-9 levels. These results suggest that miR-9 plays a role as a tumor suppressor in OSC by suppressing TLN1 expression.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cystadenoma, Serous / genetics*
  • Cystadenoma, Serous / metabolism
  • Cystadenoma, Serous / pathology
  • Disease Progression
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Grading
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Signal Transduction
  • Talin / genetics*
  • Talin / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN92 microRNA, human
  • MicroRNAs
  • TLN1 protein, human
  • Talin
  • Focal Adhesion Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt