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Trichostatin-A modulates claudin-1 mRNA stability through the modulation of Hu antigen R and tristetraprolin in colon cancer cells.
- Source :
-
Carcinogenesis . Nov2013, Vol. 34 Issue 11, p2610-2621. 12p. - Publication Year :
- 2013
-
Abstract
- Expression of claudin-1, a tight junction protein, is highly upregulated in colon cancer. We have reported that claudin-1 expression in colon cancer cells is epigenetically regulated as histone deacetylase (HDAC) inhibitors decrease claudin-1 messenger RNA (mRNA) stability and thus expression. In this regard, our data suggested a role of the 3′-untranslated region (UTR) in the regulation of HDAC-dependent regulation of claudin-1 mRNA stability. In the current study, we demonstrate, based on our continued investigation, that the ELAV-like RNA-binding proteins (RBPs), human antigen R (HuR) and tristetraprolin (TTP) associate with the 3′-UTR of claudin-1 mRNA to modulate the latter’s stability. Ribonomic and site-directed mutagenesis approaches were used to confirm the binding of HuR and TTP to the 3′-UTR of claudin-1. We further confirmed their roles in the stabilization of claudin-1 mRNA, under conditions of HDAC inhibition. In summary, we report that HuR and TTP are the critical regulators of the posttranscriptional regulation of claudin-1 expression in colon cancer cells. We also demonstrate that inhibition of HDACs by trichostatin treatment decreased the binding of HuR while increasing the binding of TTP to the 3′-UTR of claudin-1. Additionally, we provide data showing transcriptional regulation of claudin-1 expression, through the regulation of transcription factor Sp1. Taken together, we demonstrate epigenetic regulation of claudin-1 expression in colon cancer cells at the transcriptional and posttranscriptional levels. [ABSTRACT FROM PUBLISHER]
Details
- Language :
- English
- ISSN :
- 01433334
- Volume :
- 34
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 91723390
- Full Text :
- https://doi.org/10.1093/carcin/bgt207