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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 (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 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 Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Gorski, D. H. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Gorski, D. H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 31, 2007 Accepted October 15, 2007 Regulation of angiogenesis through a microRNA (miR-130a) that downregulates antiangiogenic homeobox genes GAX and HOXA5 Yun Chen and David H. Gorski* Division of Surgical Oncology, UMDNJ-Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, New Brunswick, NJ, United States * Corresponding author; email: gorskidh{at}umdnj.edu. 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'-UTR containing two miR-130a targeting sites was observed to be required for the rapid downregulation of GAX expression by serum and proangiogenic factors, while 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 downregulation 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, whose expression and antiangiogenic activity are also inhibited by miR-130a. From these data, we conclude that miR-130a is a regulator of the angiogenic phenotype of vascular endothelial cells 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: G. Sotiropoulou, G. Pampalakis, E. Lianidou, and Z. Mourelatos Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell RNA, August 1, 2009; 15(8): 1443 - 1461. [Abstract] [Full Text] [PDF] Y. Benita, H. Kikuchi, A. D. Smith, M. Q. Zhang, D. C. Chung, and R. J. Xavier An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia Nucleic Acids Res., August 1, 2009; 37(14): 4587 - 4602. [Abstract] [Full Text] [PDF] A. Bonauer, G. Carmona, M. Iwasaki, M. Mione, M. Koyanagi, A. Fischer, J. Burchfield, H. Fox, C. Doebele, K. Ohtani, et al. MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice Science, June 26, 2009; 324(5935): 1710 - 1713. [Abstract] [Full Text] [PDF] G. Boross, K. Orosz, and I. J. Farkas Human microRNAs co-silence in well-separated groups and have different predicted essentialities Bioinformatics, April 15, 2009; 25(8): 1063 - 1069. [Abstract] [Full Text] [PDF] A. Sharma, M. Kumar, J. Aich, M. Hariharan, S. K. Brahmachari, A. Agrawal, and B. Ghosh Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a PNAS, April 7, 2009; 106(14): 5761 - 5766. [Abstract] [Full Text] [PDF] Y. Suarez and W. C. Sessa MicroRNAs As Novel Regulators of Angiogenesis Circ. Res., February 27, 2009; 104(4): 442 - 454. [Abstract] [Full Text] [PDF] J. E. Fish and D. Srivastava MicroRNAs: Opening a New Vein in Angiogenesis Research Sci. Signal., January 6, 2009; 2(52): pe1 - pe1. [Abstract] [Full Text] [PDF] K. K. W. To, Z. Zhan, T. Litman, and S. E. Bates Regulation of ABCG2 Expression at the 3' Untranslated Region of Its mRNA through Modulation of Transcript Stability and Protein Translation by a Putative MicroRNA in the S1 Colon Cancer Cell Line Mol. Cell. Biol., September 1, 2008; 28(17): 5147 - 5161. [Abstract] [Full Text] [PDF] C. Urbich, A. Kuehbacher, and S. Dimmeler Role of microRNAs in vascular diseases, inflammation, and angiogenesis Cardiovasc Res, September 1, 2008; 79(4): 581 - 588. [Abstract] [Full Text] [PDF]

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