HuR, also known as Elavl1, is an RNA-binding protein that regulates embryonic 
development, progenitor cell survival, and cell stress responses. The role of 
HuR in angiogenesis is not known. Using a myeloid-specific HuR knock-out mouse 
model (Elavl1Mø KO), we show that HuR expression in bone marrow-derived 
macrophages (BMDMs) is needed to maintain the expression of genes enriched in 
AU-rich elements and U-rich elements in the 3'-UTR. In addition, BMDMs from 
Elavl1Mø KO mice also showed alterations in expression of several miRNAs. 
Interestingly, computational analysis suggested that miR-200b, which is 
up-regulated in Elavl1Mø KO BMDMs, interacts with myeloid mRNAs very close to 
the HuR binding sites, suggesting competitive regulation of gene expression. One 
such mRNA encodes vascular endothelial growth factor (VEGF)-A, a major regulator 
of angiogenesis. Immunoprecipitation of RNA-protein complexes and luciferase 
reporter assays indicate that HuR antagonizes the suppressive activity of 
miR-200b, down-regulates miR-200b expression, and promotes VEGF-A expression. 
Indeed, Vegf-a and other angiogenic regulatory transcripts were down-regulated 
in Elavl1Mø KO BMDMs. Interestingly, tumor growth, angiogenesis, vascular 
sprouting, branching, and permeability were significantly attenuated in Elavl1Mø 
KO mice, suggesting that HuR-regulated myeloid-derived factors modulate tumor 
angiogenesis in trans. Zebrafish embryos injected with an elavl1 morpholino 
oligomer or miR-200b mimic showed angiogenesis defects in the subintestinal vein 
plexus, and elavl1 mRNA rescued the repressive effect of miR-200b. In addition, 
miR-200b and HuR morpholino oligomer suppressed the activity of a zVEGF 3'-UTR 
luciferase reporter construct. Together, these studies reveal an evolutionarily 
conserved post-transcriptional mechanism involving competitive interactions 
between HuR and miR-200b that controls angiogenesis.