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

Aránzazu Chamorro-Jorganes, Elisa Araldi, Luiz O.F. Penalva, Devraj Sandhu, Carlos Fernández-Hernando, Yajaira Suárez

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

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). Methods and 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. Conclusion-: 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.

Original languageEnglish (US)
Pages (from-to)2595-2606
Number of pages12
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • angiogenesis
  • endothelium
  • microRNAs

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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