Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis

PLoS One. 2013;8(2):e56647. doi: 10.1371/journal.pone.0056647. Epub 2013 Feb 20.

Abstract

MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA levels in ovarian tissues. We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and miR-125b-inhibiting angiogenesis responses and Akt/p70S6K1/HIF-1α pathway. This study provides a rationale for new therapeutic approach to suppress tumor angiogenesis using miR-199a, miR-125b, or their mimics for ovarian cancer treatment in the future.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic / genetics*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-3 / genetics
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN125 microRNA, human
  • MicroRNAs
  • Vascular Endothelial Growth Factor A
  • mirn199 microRNA, human
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Receptor, ErbB-3