MRNA stability alterations mediated by HuR are necessary to sustain the fast growth of glioma cells

Federico Bolognani, Anne Isabelle Gallani, Lena Sokol, David S. Baskin, Nicole Meisner-Kober

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Regulation of mRNA decay is an important mechanism controlling gene expression. Steady state levels of mRNAs can be markedly altered by changes in the decay rate. The control of mRNA stability depends on sequences in the transcript itself and on RNA-binding proteins that dynamically bind to these sequences. A well characterized sequence motif, which has been shown to be present in many short-lived mRNAs, is the de-stabilizing adenylate/uridylate- rich element (ARE) located at the 30 untranslated region (30UTR) of mRNAs. HuR is an RNAbinding protein, which binds to AREs and in doing so, increases the half-life and steady state levels of the corresponding mRNA. Using tissue microarray technology, we found that HuR is over-expressed in human gliomas. We also found that there is a change in HuR localization from being solely in the nucleus to being expressed at high levels in the cytosol. Moreover, a positive correlation was found between total HuR levels, cytosolic localization and tumor grade. We also studied the decay rate of several HuR target mRNAs and found that these mRNAs have a slower rate of decay in glioma cell lines than in astrocytes. Finally, we have been able to decrease both the stability and steady state level of these transcripts in glioma cells using an RNA decoy. More importantly, the decoy transfected cells and cells exposed to a HuR inhibitor have reduced cell growth. In addition, pharmacological inhibition of HuR also resulted in glioma cell growth inhibition. In conclusion, our data suggest that post-transcriptional control abnormalities mediated by HuR are necessary to sustain the rapid growth of this devastating type of cancer.

Original languageEnglish (US)
Pages (from-to)531-542
Number of pages12
JournalJournal of Neuro-Oncology
Volume106
Issue number3
DOIs
StatePublished - Feb 1 2012

Keywords

  • Gliomas
  • HuR
  • mRNA stability
  • RNA-binding protein
  • Tissue microarray

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

Fingerprint Dive into the research topics of 'MRNA stability alterations mediated by HuR are necessary to sustain the fast growth of glioma cells'. Together they form a unique fingerprint.

Cite this