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  • Title: Mirtron microRNA-1236 inhibits VEGFR-3 signaling during inflammatory lymphangiogenesis.
    Author: Jones D, Li Y, He Y, Xu Z, Chen H, Min W.
    Journal: Arterioscler Thromb Vasc Biol; 2012 Mar; 32(3):633-42. PubMed ID: 22223733.
    Abstract:
    OBJECTIVE: Vascular endothelial growth factor receptor(VEGFR)-3 is a critical regulator of developmental and adult vasculogenesis and lymphangiogenesis through its interactions with select members of the VEGF family. The goal of this study was to investigate how VEGFR-3 expression is regulated during inflammatory lymphangiogenesis. METHODS AND RESULTS: In this study, we present for the first time evidence that VEGFR-3 can be negatively regulated by a mirtron, hsa-miR-1236 (miR-1236), which is expressed in primary human lymphatic endothelial cells. In human lymphatic endothelial cells, miR-1236 is upregulated in response to IL-1β, a negative regulator of VEGFR-3. miR-1236 binds the 3' untranslated region of Vegfr3, resulting in translational inhibition. Overexpression of miR-1236 significantly decreased expression of VEGFR-3, but not VEGFR-2, in human lymphatic endothelial cells. Compared to a control miR, overexpression of miR-1236 also led to decreased VEGFR-3 signaling. However, VEGFR-2-specific signaling was not affected. miR-1236 can attenuate human lymphatic endothelial cell migration and tube formation, as well as in vivo lymphangiogenesis. CONCLUSION: Our data suggest that miR-1236 may function as a negative regulator of VEGFR-3 signaling during inflammatory lymphangiogenesis.
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