MiR-145 reduces ADAM17 expression and inhibits in vitro migration and invasion of glioma cells

Oncol Rep. 2013 Jan;29(1):67-72. doi: 10.3892/or.2012.2084. Epub 2012 Oct 17.

Abstract

MicroRNAs are important regulators of gene expression and have been suggested to play a key role in tumorigenesis. In this study, we show that miR-145 is significantly downregulated in glioma cell lines compared to normal brain tissue and negatively regulates tumorigenesis. Restoration of miR-145 in glioma cells significantly reduced in vitro proliferation, migration and invasion. Also, overexpression of miR-145 reduced ADAM17 and EGFR expression. In addition, we tested the hypothesis that the miR-145-mediated suppression of cell proliferation, migration and invasion is, at least in part, due to silencing of ADAM17 and EGFR gene expression. Using luciferase reporters carrying the 3'-untranslated region of ADAM17 combined with western blotting, we identified ADAM17 as a direct target of miR-145. Collectively, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor proliferation, but also cell migration and invasion, and warrants further investigation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • ADAM17 Protein
  • Apoptosis
  • Blotting, Western
  • Brain / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • In Vitro Techniques
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Luciferases
  • EGFR protein, human
  • ErbB Receptors
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human