title: MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A.
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.
authors.affiliation: Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Theodor Stern-Kai 7, Frankfurt, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Urbich
authors.forename: David
authors.initials: D
authors.lastname: Kaluza
authors.forename: Timo
authors.initials: T
authors.lastname: Frömel
authors.forename: Andrea
authors.initials: A
authors.lastname: Knau
authors.forename: Katrin
authors.initials: K
authors.lastname: Bennewitz
authors.forename: Reinier A
authors.initials: RA
authors.lastname: Boon
authors.forename: Angelika
authors.initials: A
authors.lastname: Bonauer
authors.forename: Carmen
authors.initials: C
authors.lastname: Doebele
authors.forename: Jes-Niels
authors.initials: JN
authors.lastname: Boeckel
authors.forename: Eduard
authors.initials: E
authors.lastname: Hergenreider
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Jens
authors.initials: J
authors.lastname: Kroll
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fleming
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000196:embryology / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C504201:SEMA6A protein, human; D039961:Semaphorins