MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A - PubMed (original) (raw)

. 2012 Feb 9;119(6):1607-16.

doi: 10.1182/blood-2011-08-373886. Epub 2011 Dec 19.

David Kaluza, Timo Frömel, Andrea Knau, Katrin Bennewitz, Reinier A Boon, Angelika Bonauer, Carmen Doebele, Jes-Niels Boeckel, Eduard Hergenreider, Andreas M Zeiher, Jens Kroll, Ingrid Fleming, Stefanie Dimmeler

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MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A

Carmen Urbich et al. Blood. 2012.

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Abstract

MicroRNAs (miRs) are small RNAs that regulate gene expression at the posttranscriptional level. miR-27 is expressed in endothelial cells, but the specific functions of miR-27b and its family member miR-27a are largely unknown. Here we demonstrate that overexpression of miR-27a and miR-27b significantly increased endothelial cell sprouting. Inhibition of both miR-27a and miR-27b impaired endothelial cell sprout formation and induced endothelial cell repulsion in vitro. In vivo, inhibition of miR-27a/b decreased the number of perfused vessels in Matrigel plugs and impaired embryonic vessel formation in zebrafish. Mechanistically, miR-27 regulated the expression of the angiogenesis inhibitor semaphorin 6A (SEMA6A) in vitro and in vivo and targeted the 3'-untranslated region of SEMA6A. Silencing of SEMA6A partially reversed the inhibition of endothelial cell sprouting and abrogated the repulsion of endothelial cells mediated by miR-27a/b inhibition, indicating that SEMA6A is a functionally relevant miR-27 downstream target regulating endothelial cell repulsion. In summary, we show that miR-27a/b promotes angiogenesis by targeting the angiogenesis inhibitor SEMA6A, which controls repulsion of neighboring endothelial cells.

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