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

Yun Chen, David H. Gorski

Research output: Contribution to journalArticle

345 Citations (Scopus)

Abstract

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 downregulation 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 psi-CHECK2-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.

Original languageEnglish (US)
Pages (from-to)1217-1226
Number of pages10
JournalBlood
Volume111
Issue number3
DOIs
StatePublished - 2008
Externally publishedYes

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Homeobox Genes
3' Untranslated Regions
MicroRNAs
Endothelial cells
Down-Regulation
Genes
Endothelial Cells
Serum
Luciferases
Reporter Genes
Tumors
Binding Sites
Genome
Phenotype
Gene Expression
Neoplasms

ASJC Scopus subject areas

  • Hematology

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Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. / Chen, Yun; Gorski, David H.

In: Blood, Vol. 111, No. 3, 2008, p. 1217-1226.

Research output: Contribution to journalArticle

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