Transcriptional down-regulation of IGFBP-3 in human hepatocellular carcinoma cells is mediated by the binding of TIA-1 to its AT-rich element in the 3'-untranslated region

Cancer Lett. 2010 Nov 28;297(2):259-68. doi: 10.1016/j.canlet.2010.05.019. Epub 2010 Jul 6.

Abstract

Insulin-like growth factor binding protein-3 (IGFBP-3) plays key roles in regulating cell growth, differentiation, and apoptosis in a variety of cellular systems. We have observed significant down-regulation of IGFBP-3 expression in primary human hepatocellular carcinoma (HCC) tissues when compared to adjacent histologically normal tissues. In this study, we functionally mapped the entire 3'-UTR of the IGFBP-3 mRNA, spanning 1471 nt and identified a 210 bp fragment consisting of AT-rich elements at the distal downstream region preceding the consensus pre-mRNA polyadenylation signal that provide high affinity binding for TIA-1 to mediate the specific suppression of IGFBP-3 expression in human HCC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • AT Rich Sequence*
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / biosynthesis
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Poly(A)-Binding Proteins / genetics
  • Poly(A)-Binding Proteins / metabolism*
  • Promoter Regions, Genetic
  • T-Cell Intracellular Antigen-1
  • Transfection

Substances

  • 3' Untranslated Regions
  • Insulin-Like Growth Factor Binding Protein 3
  • Poly(A)-Binding Proteins
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human