Tristetraprolin regulates prostate cancer cell growth through suppression of E2F1

J Microbiol Biotechnol. 2014 Feb 28;24(2):287-94. doi: 10.4014/jmb.1309.09070.

Abstract

The transcription factor E2F1 is active during G1 to S transition and is involved in the cell cycle and progression. A recent study reported that increased E2F1 is associated with DNA damage and tumor development in several tissues using transgenic models. Here, we show that E2F1 expression is regulated by tristetraprolin (TTP) in prostate cancer. Overexpression of TTP decreased the stability of E2F1 mRNA and the expression level of E2F1. In contrast, inhibition of TTP using siRNA increased the E2F1 expression. E2F1 mRNA contains three AREs within the 3'UTR, and TTP destabilized a luciferase mRNA that contained the E2F1 mRNA 3'UTR. Analyses of point mutants of the E2F1 mRNA 3'UTR demonstrated that ARE2 was mostly responsible for the TTP-mediated destabilization of E2F1 mRNA. RNA EMSA revealed that TTP binds directly to the E2F1 mRNA 3'UTR of ARE2. Moreover, treatment with siRNA against TTP increased the proliferation of PC3 human prostate cancer cells. Taken together, these results demonstrate that E2F1 mRNA is a physiological target of TTP and suggests that TTP controls proliferation as well as migration and invasion through the regulation of E2F1 mRNA stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Proliferation*
  • DNA Mutational Analysis
  • E2F1 Transcription Factor / antagonists & inhibitors*
  • Gene Expression Regulation*
  • Gene Silencing
  • Humans
  • Male
  • Point Mutation
  • Prostatic Neoplasms / physiopathology*
  • RNA Stability
  • Tristetraprolin / metabolism*

Substances

  • 3' Untranslated Regions
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Tristetraprolin
  • ZFP36 protein, human