Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5

Blood. 2008 Feb 1;111(3):1217-26. doi: 10.1182/blood-2007-07-104133. Epub 2007 Oct 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Angiogenesis Inhibitors / genetics*
  • Base Sequence
  • Binding Sites
  • Cells, Cultured
  • Down-Regulation / genetics*
  • Endothelial Cells / metabolism
  • Gene Expression
  • Genes, Reporter / genetics
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Serum
  • Umbilical Cord / metabolism


  • 3' Untranslated Regions
  • Angiogenesis Inhibitors
  • HOXA5 protein, human
  • Homeodomain Proteins
  • MEOX2 protein, human
  • MicroRNAs