Buchumschlag

Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells

MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a, and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identifi...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Döbele, Carmen (VerfasserIn) , Bonauer, Angelika (VerfasserIn) , Fischer, Ariane (VerfasserIn) , Scholz, Alexander (VerfasserIn) , Reiss, Yvonne (VerfasserIn) , Urbich, Carmen (VerfasserIn) , Hofmann, Wolf-Karsten (VerfasserIn) , Zeiher, Andreas M. (VerfasserIn) , Dimmeler, Stefanie (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: March 18, 2010
In: Blood
Year: 2010, Jahrgang: 115, Heft: 23, Pages: 4944-4950
ISSN:1528-0020
DOI:10.1182/blood-2010-01-264812
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2010-01-264812
Volltext
Verfasserangaben:Carmen Doebele, Angelika Bonauer, Ariane Fischer, Alexander Scholz, Yvonne Reiss, Carmen Urbich, Wolf-Karsten Hofmann, Andreas M. Zeiher, and Stefanie Dimmeler
Beschreibung
Zusammenfassung:MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a, and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, -19a, and -20a significantly inhibited 3-dimensional spheroid sprouting in vitro, whereas inhibition of miR-17, -18a, and -20a augmented endothelial cell sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in Matrigel plugs, whereas antagomirs that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several proangiogenic genes. Specifically, Janus kinase 1 was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell-intrinsic antiangiogenic activity in endothelial cells. Inhibition of miR-17/20 specifically augmented neovascularization of Matrigel plugs but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo.
Beschreibung:Gesehen am 15.05.2023
Beschreibung:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2010-01-264812

Ähnliche Einträge