title: Regulation of vascular endothelial growth factor signaling by miR-200b.
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.
authors.affiliation: Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea.
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Choi
authors.forename: Sena
authors.initials: S
authors.lastname: Yoon
authors.forename: Yongsu
authors.initials: Y
authors.lastname: Jeong
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Yoon
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Baek
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003094:Collagen; D004338:Drug Combinations; D004730:Endothelium, Vascular; D004797:Enzyme-Linked Immunosorbent Assay; D017930:Genes, Reporter; D006801:Humans; D007797:Laminin; D008156:Luciferases / Q000032:analysis; D035683:MicroRNAs / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D010957:Plasmids; D011509:Proteoglycans; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D007797:Laminin; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D011509:Proteoglycans; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen; D008156:Luciferases; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3