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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
Statement of
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
Mice, Inbred C57BL
Homeodomain Proteins
Tumor Suppressor Proteins
RNA, Messenger
3' Untranslated Regions
DNA Primers
Binding Sites
Base Sequence
Sequence Homology, Nucleic Acid
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:
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