miR-191 suppresses angiogenesis by activation of NF-κB signaling

MicroRNAs (miRNAs) are powerful regulators of diverse biologic processes. However, the function of most miRNAs in angiogenesis remains elusive. In this study, we identified miR-191-5p (miR-191) as a potent inhibitor of blood vessel development. Transfection of human dermal microvascular endothelial cells with miR-191 mimic (miR-191m) inhibited their proliferation, migration, and tube formation. Moreover, vascular sprouting of miR-191m-transfected mouse aortic rings was significantly reduced when compared with controls. Transfection with miR-191 inhibitor (miR-191i) induced proangiogenic effects. The anti-and proangiogenic activities of miR-191m and -191i were further demonstrated in vivo. Additional molecular biologic analyses revealed that miR-191m activates NF-kappa B signaling by up-regulating the mRNA expression of p65. miR-191 also increased the mRNA levels of the antiangiogenic factors p21 and tissue inhibitor of metalloproteinase-1 and reduced the expression of the proangiogenic factors eNOS and matrix metalloproteinase-1 and -9. Blockade of NF-kB activation with Bay 11-7082 reversed the antiangiogenic effects of miR-191m. These findings indicate that miR-191 effectively suppresses angiogenesis by activation of the NF-kB signaling pathway.