MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A
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 significan...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2012
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| In: |
Blood
Year: 2012, Jahrgang: 119, Heft: 6, Pages: 1607-1616 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2011-08-373886 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1182/blood-2011-08-373886 Verlag, Volltext: http://www.bloodjournal.org/content/119/6/1607 
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| Verfasserangaben: | 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 |
| Zusammenfassung: | 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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| Beschreibung: | Prepublished online as Blood first edition paper, December 19, 2011 Gesehen am 21.02.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2011-08-373886 |