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

• Verfasst von: Döbele, Carmen [VerfasserIn]
• Verfasst von: Bonauer, Angelika [VerfasserIn]
• Verfasst von: Fischer, Ariane [VerfasserIn]
• Verfasst von: Scholz, Alexander [VerfasserIn]
• Verfasst von: Reiss, Yvonne [VerfasserIn]
• Verfasst von: Urbich, Carmen [VerfasserIn]
• Verfasst von: Hofmann, Wolf-Karsten [VerfasserIn]
• Verfasst von: Zeiher, Andreas M. [VerfasserIn]
• Verfasst von: Dimmeler, Stefanie [VerfasserIn]
• Titel: Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells
• Verf.angabe: Carmen Doebele, Angelika Bonauer, Ariane Fischer, Alexander Scholz, Yvonne Reiss, Carmen Urbich, Wolf-Karsten Hofmann, Andreas M. Zeiher, and Stefanie Dimmeler
• E-Jahr: 2010
• Jahr: March 18, 2010
• Umfang: 7 S.
• Fussnoten: Gesehen am 15.05.2023
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2010
• Band/Heft Quelle: 115(2010), 23 vom: Juni, Seite 4944-4950
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood-2010-01-264812
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1845370848

Abstract

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.