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

Bolognani, Federico and Gallani, Anne-Isabelle and Sokol, Lena and Baskin, David and Meisner Kober, Nicole-Claudia (2012) mRNA stability alterations mediated by HuR are necessary to sustain the fast growth of glioma cells. Journal of Neuro-Oncology, 106 (3). pp. 531-542. ISSN 0167-594X

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 AU-rich element (ARE) located at the 3’untranslated region (3’UTR) of mRNAs. HuR is an RNA-binding 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.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used author can archive post-print
Keywords: HuR, glioma, mRNA stability, tissue microarray, RNA-binding protein
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/5318

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