Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1) in Colorectal Cancer Cells.
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.
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Cyril.Sobolewski@unige.ch.
Cyril
C
Sobolewski
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. sandhyasanduja@gmail.com.
Sandhya
S
Sanduja
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Fernando.Blanco@jefferson.edu.
Fernando F
FF
Blanco
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. lyhukk@yahoo.com.
Liangyan
L
Hu
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. ddixon3@kumc.edu.
Dan A
DA
Dixon
D020148:Butyric Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*; D000077337:Vorinostat
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D051816:Tristetraprolin; D020148:Butyric Acid; C012589:trichostatin A; D000077337:Vorinostat; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
COX-2; HDAC; TTP; colon cancer; post-transcriptional regulation