Regulation of vascular endothelial growth factor signaling by miR-200b

Mol Cells. 2011 Jul;32(1):77-82. doi: 10.1007/s10059-011-1042-2. Epub 2011 May 2.

Abstract

Vascular endothelial growth factor (VEGF) signaling plays an important role in angiogenesis. In the VEGF signaling pathway, the key components are VEGF and its receptors, Flt-1 and KDR. In this study, we show that transfection of synthetic miR-200b reduced protein levels of VEGF, Flt-1, and KDR. In A549 cells, miR-200b targeted the predicted binding sites in the 3'-untranslated region (3'-UTR) of VEGF, Flt-1, and KDR as revealed by a luciferase reporter assay. When transfected with miR-200b, the ability of HUVECs to form a capillary tube on Matrigel and VEGF-induced phosphorylation of ERK1/2 were significantly reduced. Taken together, these results suggest that miR-200b negatively regulates VEGF signaling by targeting VEGF and its receptors and that miR-200b may have therapeutic potential as an angiogenesis inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Angiogenesis Inhibitors / genetics*
  • Blotting, Western
  • Cell Line, Tumor
  • Collagen
  • Drug Combinations
  • Endothelium, Vascular
  • Enzyme-Linked Immunosorbent Assay
  • Genes, Reporter
  • Humans
  • Laminin
  • Luciferases / analysis
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Phosphorylation / genetics
  • Plasmids
  • Proteoglycans
  • Signal Transduction / genetics*
  • Transfection
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • 3' Untranslated Regions
  • Angiogenesis Inhibitors
  • Drug Combinations
  • Laminin
  • MIRN200 microRNA, human
  • MicroRNAs
  • Proteoglycans
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • matrigel
  • Collagen
  • Luciferases
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3