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...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 18, 2010
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| In: |
Blood
Year: 2010, Volume: 115, Issue: 23, Pages: 4944-4950 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2010-01-264812 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2010-01-264812
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| Author Notes: | Carmen Doebele, Angelika Bonauer, Ariane Fischer, Alexander Scholz, Yvonne Reiss, Carmen Urbich, Wolf-Karsten Hofmann, Andreas M. Zeiher, and Stefanie Dimmeler |
| Summary: | 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. |
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| Item Description: | Gesehen am 15.05.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2010-01-264812 |