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
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Angiogenesis Inhibitors / genetics*
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Blotting, Western
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Cell Line, Tumor
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Collagen
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Drug Combinations
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Endothelium, Vascular
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Enzyme-Linked Immunosorbent Assay
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Genes, Reporter
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Humans
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Laminin
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Luciferases / analysis
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MicroRNAs / genetics*
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism*
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Neoplasms / genetics
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Neoplasms / metabolism
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism*
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Phosphorylation / genetics
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Plasmids
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Proteoglycans
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Signal Transduction / genetics*
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Transfection
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Vascular Endothelial Growth Factor A / antagonists & inhibitors*
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
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Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-1 / metabolism
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
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Vascular Endothelial Growth Factor Receptor-2 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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3' Untranslated Regions
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Angiogenesis Inhibitors
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Drug Combinations
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Laminin
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MIRN200 microRNA, human
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MicroRNAs
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Proteoglycans
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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matrigel
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Collagen
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Luciferases
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3