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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1217-1226. Prepublished online as a Blood First Edition Paper on October 23, 2007; DOI 10.1182/blood-2007-07-104133. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-104133v1 111/3/1217    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Chen, Y. Articles by Gorski, D. H. PubMed PubMed Citation Articles by Chen, Y. Articles by Gorski, D. H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5 Yun Chen1, and David H. Gorski1 1 Division of Surgical Oncology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, New Brunswick Angiogenesis is critical to tumor progression. The homeobox gene GAX inhibits angiogenesis in vascular endothelial cells (ECs). We have identified a microRNA (miR-130a) that regulates GAX expression and hypothesized that it plays a major role in modulating GAX activity in ECs. A 280-bp fragment from the GAX 3'-untranslated region (3'-UTR) containing 2 miR-130a targeting sites was observed to be required for the rapid down-regulation of GAX expression by serum and proangiogenic factors, whereas the activity of the GAX promoter did not vary with exposure to serum or proangiogenic factors. This same 280-bp sequence in the GAX 3'-UTR cloned into the psiCHECK2-Luciferase vector mediated serum-induced down-regulation of the reporter gene when placed 3' of it. Finally, forced expression of miR-130a inhibits GAX expression through this specific GAX 3'-UTR sequence. A genome-wide search for other possible miR-130a binding sites revealed an miR-130a targeting site in the 3'-UTR of the antiangiogenic homeobox gene HOXA5, the expression and antiangiogenic activity of which are also inhibited by miR-130a. From these data, we conclude that miR-130a is a regulator of the angiogenic phenotype of vascular ECs largely through its ability to modulate the expression of GAX and HOXA5. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Urbich, A. Kuehbacher, and S. Dimmeler Role of microRNAs in vascular diseases, inflammation, and angiogenesis Cardiovasc Res, July 1, 2008; (2008) cvn156v2. [Abstract] [Full Text] [PDF]

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