HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium

Br J Cancer. 2011 Mar 1;104(5):819-29. doi: 10.1038/bjc.2011.20. Epub 2011 Feb 1.


Background: Tumour stromal cells differ from its normal counterpart. We have shown that tumour endothelial cells (TECs) isolated from tumour tissues are also abnormal. Furthermore, we found that mRNAs of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) were upregulated in TECs. Vascular endothelial growth factor-A and COX-2 are angiogenic factors and their mRNAs contain an AU-rich element (ARE). AU-rich element-containing mRNAs are reportedly stabilised by Hu antigen R (HuR), which is exported to the cytoplasm.

Methods: Normal endothelial cell (NEC) and two types of TECs were isolated. We evaluated the correlation of HuR and accumulation of VEGF-A and COX-2 mRNAs in TECs and effects of HuR on biological phenotypes of TECs.

Results: The HuR protein was accumulated in the cytoplasm of TECs, but not in NECs. Vascular endothelial growth factor-A and COX-2 mRNA levels decreased due to HuR knockdown and it was shown that these ARE-mRNA were bound to HuR in TECs. Furthermore, HuR knockdown inhibited cell survival, random motility, tube formation, and Akt phosphorylation in TECs.

Conclusion: Hu antigen R is associated with the upregulation of VEGF-A and COX-2 mRNA in TECs, and has an important role in keeping an angiogenic switch on, through activating angiogenic phenotype in tumour endothelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Antigens, Surface / pharmacology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Melanoma / blood supply
  • Mouth Neoplasms / blood supply
  • Neoplasms / blood supply*
  • Phosphorylation
  • RNA, Messenger
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • RNA-Binding Proteins / pharmacology*
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism


  • Antigens, Surface
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2