Hypoxic regulation of stability of connective tissue growth factor/CCN2 mRNA by 3'-untranslated region interacting with a cellular protein in human chondrosarcoma cells

Oncogene. 2006 Feb 16;25(7):1099-110. doi: 10.1038/sj.onc.1209129.


Connective tissue growth factor (CTGF/CCN2) can be induced by various forms of stress such as exposure to high glucose, mechanical load, or hypoxia. Here, we investigated the molecular mechanism involved in the induction of ctgf/ccn2 by hypoxia in a human chondrosarcoma cell line, HCS-2/8. Hypoxia increased the ctgf/ccn2 mRNA level by altering the 3'-untranslated region (UTR)-mediated mRNA stability without requiring de novo protein synthesis. After a series of extensive analyses, we eventually found that the cis-repressive element of 84 bases within the 3'-UTR specifically bound to a cytoplasmic/nuclear protein. By conducting a UV crosslinking assay, we found the cytoplasmic/nuclear protein to be a 35 kDa molecule that bound to the cis-element in a hypoxia-inducible manner. These results suggest that a cis-element in the 3'-UTR of ctgf/ccn2 mRNA and trans-factor counterpart(s) play an important role in the post-transcriptional regulation by determining the stability of ctgf/ccn2 mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / metabolism*
  • Animals
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Cell Hypoxia
  • Chondrosarcoma / genetics*
  • Chondrosarcoma / metabolism
  • Connective Tissue Growth Factor
  • Cytoplasm / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Mice, Nude
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic
  • Protein Biosynthesis
  • RNA Stability*
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured


  • 3' Untranslated Regions
  • CCN2 protein, human
  • CCN2 protein, mouse
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Connective Tissue Growth Factor