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

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.

• Authors: Cyril Sobolewski, Sandhya Sanduja, Fernando F Blanco, Liangyan Hu, Dan A Dixon
• Journal: Biomolecules (Biomolecules) Vol. 5 Issue 3 Pg. 2035-55 (Aug 28 2015) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 26343742 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• EGR1 protein, human
• Early Growth Response Protein 1
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• RNA, Messenger
• Tristetraprolin
• Butyric Acid
• trichostatin A
• Vorinostat
• Cyclooxygenase 2
• PTGS2 protein, human

Topics

• Butyric Acid (pharmacology)
• Cell Line, Tumor
• Colorectal Neoplasms (metabolism)
• Cyclooxygenase 2 (genetics, metabolism)
• Early Growth Response Protein 1 (metabolism)
• Epigenesis, Genetic
• Histone Deacetylase Inhibitors (pharmacology)
• Humans
• Hydroxamic Acids (pharmacology)
• RNA, Messenger (metabolism)
• Tristetraprolin (genetics, metabolism)
• Vorinostat