OBJECTIVE microRNAs play key roles in modulating a variety of cellular processes by post-transcriptional regulation of their target genes. VEGF, VEGFR-2 and FGFR-1 were identified by bioinformatic approaches and subsequently validated as targets of miR-16 and miR-424 in endothelial cells (ECs). RESULTS/METHODS Mimetics of these microRNAs reduced VEGF, VEGFR-2 and FGFR-1 expression, whereas specific antagonists enhanced their expression. Expression of mature miR-16 and miR-424 was up-regulated upon VEGF or bFGF treatment. This up-regulation was accompanied by a parallel increase in pri-miR-16-1 and pri-miR-16-2 but not in pri-miR-424 levels, indicating a VEGF/bFGF-dependent transcriptional and post-transcriptional 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 finely 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.

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