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

Biomolecules
Cyril SobolewskiDan A Dixon

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.

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Citations

May 20, 2016·Intractable & Rare Diseases Research·Jing TianGuosheng Jiang
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Nov 20, 2021·The FEBS Journal·Madeleine R Smith, Guilherme Costa

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Methods Mentioned

BETA
acetylation
PCR
immunoprecipitation
transfection
ChIP
histone acetylation
tissue array
Transfections
Assay
protein assay

Software Mentioned

ImageJ
Quantity One Analysis

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