miR-195 inhibits tumor growth and angiogenesis through modulating IRS1 in breast cancer

Biomed Pharmacother. 2016 May;80:95-101. doi: 10.1016/j.biopha.2016.03.007. Epub 2016 Mar 17.

Abstract

Angiogenesis has been found as an attractive target for drug therapy as it is necessary for tumor growth. Accumulating evidences show that microRNAs (miRNAs), which are a group of highly conserved, single-stranded, short non-coding RNAs, play important roles through directly targeting angiogenic factors and protein kinases. The purpose of this study is to investigate the role of miR-195 in breast cancer development and angiogenesis through targeting IRS1. We show that miR-195 is inversely related with Insulin receptor substrate 1 (IRS1) in both breast cancer cells and breast cancer tissues. Induction of miR-195 could suppress IRS1 protein expression through binding to its 3'UTR regions either by transfection with miR-195 oligo or by infection with lentivirus encoding miR-195 gene. Moreover, re-expression of IRS1 reverses miR-195-mediated repression of tumor cell growth and miR-195 inhibits tumor angiogenesis through suppressing IRS1-VEGF axis. These data suggest that miR-195 mimics are potential therapeutic agents for breast cancer diagnose.

Keywords: Angiogenesis; Breast cancer; Insulin receptor substrate 1; MiR-195.

MeSH terms

  • Animals
  • Base Sequence
  • Breast Neoplasms / blood supply*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Chickens
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Insulin Receptor Substrate Proteins / genetics*
  • Insulin Receptor Substrate Proteins / metabolism
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic / genetics*
  • Reproducibility of Results

Substances

  • Insulin Receptor Substrate Proteins
  • MIRN195 microRNA, human
  • MicroRNAs