title: MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1.
abstract: OBJECTIVE
  MicroRNAs play key roles in modulating a variety of cellular processes by posttranscriptional regulation of their target genes. Vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2), and fibroblast growth factor receptor-1 (FGFR1) were identified by bioinformatic approaches and subsequently validated as targets of microRNA (miR)-16 and miR-424 in endothelial cells (ECs).
  
  
  RESULTS
  Mimetics of these microRNAs reduced VEGF, VEGFR2, and FGFR1 expression, whereas specific antagonists enhanced their expression. Expression of mature miR-16 and miR-424 was upregulated on VEGF or basic fibroblast growth factor (bFGF) treatment. This upregulation was accompanied by a parallel increase in primary transcript (pri-miR)-16-1 and pri-miR-16-2 but not in pri-miR-424 levels, indicating a VEGF/bFGF-dependent transcriptional and posttranscriptional regulation of miR-16 and miR-424, respectively. Reduced expression of VEGFR2 and FGFR1 by miR-16 or miR-424 overexpression regulated VEGF and bFGF signaling through these receptors, thereby affecting the activity of downstream components of the pathways. Functionally, miR-16 or miR-424 overexpression reduced proliferation, migration, and cord formation of ECs in vitro, and lentiviral overexpression of miR-16 reduced the ability of ECs to form blood vessels in vivo.
  
  
  CONCLUSIONS
  We conclude that these miRNAs fine-tune the expression of selected endothelial angiogenic mediators in response to these growth factors. Altogether, these findings suggest that miR-16 and miR-424 play important roles in regulating cell-intrinsic angiogenic activity of ECs.
authors: Department of Medicine and Cell Biology, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Aránzazu
authors: A
authors: Chamorro-Jorganes
authors: Elisa
authors: E
authors: Araldi
authors: Luiz O F
authors: LO
authors: Penalva
authors: Devraj
authors: D
authors: Sandhu
authors: Carlos
authors: C
authors: Fernández-Hernando
authors: Yajaira
authors: Y
authors: Suárez
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology; D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; C505362:MIRN16 microRNA, human; C554214:MIRN424 microrna, human; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D040301:Vascular Endothelial Growth Factor Receptor-2