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

• Verfasst von: Urbich, Carmen [VerfasserIn]
• Verfasst von: Bennewitz, Katrin [VerfasserIn]
• Verfasst von: Kroll, Jens [VerfasserIn]
• Titel: MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A
• Verf.angabe: Carmen Urbich, 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
• Umfang: 10 S.
• Fussnoten: Prepublished online as Blood first edition paper, December 19, 2011 ; Gesehen am 21.02.2019
• Titel Quelle: Enthalten in: Blood
• Jahr Quelle: 2012
• Band/Heft Quelle: 119(2012), 6, S. 1607-1616
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood-2011-08-373886
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 158787251X

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.