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Prox1 expression is negatively regulated by miR-181 in endothelial cells

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dc.contributor.authorKazenwadel, J.
dc.contributor.authorMichael, M.
dc.contributor.authorHarvey, N.
dc.date.issued2010
dc.description.abstractThe 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.
dc.description.statementofresponsibilityJan Kazenwadel, Michael Z. Michael and Natasha L. Harvey
dc.identifier.citationBlood, 2010; 116(13):2395-2401
dc.identifier.doi10.1182/blood-2009-12-256297
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.orcidKazenwadel, J. [0000-0001-6216-3444]
dc.identifier.orcidHarvey, N. [0000-0001-9839-8966]
dc.identifier.urihttp://hdl.handle.net/2440/61763
dc.language.isoen
dc.publisherAmer Soc Hematology
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/453493
dc.rights© 2010 by The American Society of Hematology
dc.source.urihttps://doi.org/10.1182/blood-2009-12-256297
dc.subjectlymphatic vasculature
dc.subjectblood
dc.subjectgene
dc.subjectmicrornas
dc.titleProx1 expression is negatively regulated by miR-181 in endothelial cells
dc.typeJournal article
pubs.publication-statusPublished

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