Tristetraprolin inhibits the growth of human glioma cells through downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor mRNAs

Mol Cells. 2015;38(2):156-62. doi: 10.14348/molcells.2015.2259. Epub 2014 Dec 30.

Abstract

Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Downregulatoion of the uPA and uPAR has been reported to inhibit the growth glioblastoma. Here, we demonstrate that tristetraprolin (TTP) inhibits the growth of U87MG human glioma cells through downregulation of uPA and uPAR. Our results show that expression level of TTP is inversely correlated with those of uPA and uPAR in human glioma cells and tissues. TTP binds to the AU-rich elements within the 3' untranslated regions of uPA and uPAR and overexpression of TTP decreased the expression of uPA and uPAR through enhancing the degradation of their mRNAs. In addition, overexpression of TTP inhibited the growth and invasion of U87MG cells. Our findings implicate that TTP can be used as a promising therapeutic target to treat human glioma.

Keywords: TTP; glioma; uPA; uPAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Humans
  • Receptors, Urokinase Plasminogen Activator / genetics*
  • Tristetraprolin / pharmacology*
  • Urokinase-Type Plasminogen Activator / genetics*

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • Receptors, Urokinase Plasminogen Activator
  • Tristetraprolin
  • Urokinase-Type Plasminogen Activator