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Biomolecules 2015, 5(3), 2035-2055; doi:10.3390/biom5032035

Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1) in Colorectal Cancer Cells

Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: André P. Gerber
Received: 21 May 2015 / Revised: 30 July 2015 / Accepted: 10 August 2015 / Published: 28 August 2015
(This article belongs to the Special Issue RNA-Binding Proteins—Structure, Function, Networks and Disease)
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Abstract

The RNA-binding protein tristetraprolin (TTP) promotes rapid decay of mRNAs bearing 3' UTR AU-rich elements (ARE). In many cancer types, loss of TTP expression is observed allowing for stabilization of ARE-mRNAs and their pathologic overexpression. Here we demonstrate that histone deacetylase (HDAC) inhibitors (Trichostatin A, SAHA and sodium butyrate) promote TTP expression in colorectal cancer cells (HCA-7, HCT-116, Moser and SW480 cells) and cervix carcinoma cells (HeLa). We found that HDAC inhibitors-induced TTP expression, promote the decay of COX-2 mRNA, and inhibit cancer cell proliferation. HDAC inhibitors were found to promote TTP transcription through activation of the transcription factor Early Growth Response protein 1 (EGR1). Altogether, our findings indicate that loss of TTP in tumors occurs through silencing of EGR1 and suggests a therapeutic approach to rescue TTP expression in colorectal cancer. View Full-Text
Keywords: HDAC; TTP; post-transcriptional regulation; COX-2; colon cancer HDAC; TTP; post-transcriptional regulation; COX-2; colon cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Sobolewski, C.; Sanduja, S.; Blanco, F.F.; Hu, L.; Dixon, D.A. Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1) in Colorectal Cancer Cells. Biomolecules 2015, 5, 2035-2055.

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