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https://hdl.handle.net/2440/61763
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Type: | Journal article |
Title: | Prox1 expression is negatively regulated by miR-181 in endothelial cells |
Author: | Kazenwadel, J. Michael, M. Harvey, N. |
Citation: | Blood, 2010; 116(13):2395-2401 |
Publisher: | Amer Soc Hematology |
Issue Date: | 2010 |
ISSN: | 0006-4971 1528-0020 |
Statement of Responsibility: | Jan Kazenwadel, Michael Z. Michael and Natasha L. Harvey |
Abstract: | The specification of arterial, venous, and lymphatic endothelial cell fate is critical during vascular development. Although the homeobox transcription factor, Prox1, is crucial for the specification and maintenance of lymphatic endothelial cell identity, little is known regarding the mechanisms that regulate Prox1 expression. Here we demonstrate that miR-181a binds the 3' untranslated region of Prox1, resulting in translational inhibition and transcript degradation. Increased miR-181a activity in primary embryonic lymphatic endothelial cells resulted in substantially reduced levels of Prox1 mRNA and protein and reprogramming of lymphatic endothelial cells toward a blood vascular phenotype. Conversely, treatment of primary embryonic blood vascular endothelial cells with miR-181a antagomir resulted in increased Prox1 mRNA levels. miR-181a expression is significantly higher in embryonic blood vascular endothelial cells compared with lymphatic endothelial cells, suggesting that miR-181 activity could be an important mechanism by which Prox1 expression is silenced in the blood vasculature during development. Our work is the first example of a microRNA that targets Prox1 and has implications for the control of Prox1 expression during vascular development and neo-lymphangiogenesis. |
Keywords: | Cells, Cultured Hela Cells Endothelial Cells Animals Mice, Inbred C57BL Humans Mice Homeodomain Proteins Tumor Suppressor Proteins MicroRNAs RNA, Messenger 3' Untranslated Regions DNA Primers Transfection Down-Regulation Binding Sites Base Sequence Sequence Homology, Nucleic Acid Lymphangiogenesis Neovascularization, Physiologic Molecular Sequence Data Embryonic Stem Cells |
Rights: | © 2010 by The American Society of Hematology |
DOI: | 10.1182/blood-2009-12-256297 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/453493 |
Published version: | http://dx.doi.org/10.1182/blood-2009-12-256297 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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