Prevention of murine experimental corneal trauma by epigenetic events regulating claudin 6 and claudin 9

Nishikiori, Nami; Sawada, Norimasa; Ohguro, Hiroshi

doi:10.1007/s10384-008-0524-z

Cited by 10 publications

(8 citation statements)

References 44 publications

(32 reference statements)

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“…Reasons for such selectivity are not clearly understood; however, genes downregulated on HDAC inhibition are primarily considered tumor promoters. Importantly, studies have reported epigenetic regulation of specific claudin family members in cancer (25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Trichostatin-A modulates claudin-1 mRNA stability through the modulation of Hu antigen R and tristetraprolin in colon cancer cells

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 99%

Trichostatin-A modulates claudin-1 mRNA stability through the modulation of Hu antigen R and tristetraprolin in colon cancer cells

et al. 2013

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“…We have also shown a positive correlation of claudin-1 expression with colon tumor progression, invasion and metastasis (Dhawan et al , 2005). Other studies have shown epigenetic regulation of specific claudin family members (Honda et al , 2007; Nishikiori et al , 2008) in addition to occludin and its correlation with tumorigenicity of cancer cells (Osanai et al , 2007b). HDACI suppress activities of multiple HDACs that lead to increased histone acetylation and thus modulate expression of specific genes involved in growth arrest, differentiation and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

HDAC inhibitors regulate claudin-1 expression in colon cancer cells through modulation of mRNA stability

et al. 2009

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Expression and cellular distribution of claudin-1, a tight junction protein, is dysregulated in colon cancer and its overexpression in colon cancer cells induced dedifferentiation and increased invasion. However, the molecular mechanism(s) underlying dysregulated claudin-1 expression in colon cancer remains poorly understood. Histone deacetylase (HDAC)-dependent histone acetylation is an important mechanism of the regulation of cancer-related genes and inhibition of HDACs induces epithelial differentiation and decreased invasion. Therefore, in this study, we examined the role of HDAC-dependent epigenetic regulation of claudin-1 in colon cancer. In this study, we show that sodium butyrate and Trichostatin A (TSA), two structurally different and widely used HDAC inhibitors, inhibited claudin-1 expression in multiple colon cancer cell lines. Further studies revealed modulation of claudin-1 mRNA stability by its 3′-UTR as the major mechanism underlying HDAC-dependent claudin-1 expression. In addition, overexpression of claudin-1 abrogated the TSA-induced inhibition of invasion in colon cancer cells suggesting functional crosstalk. Analysis of mRNA expression in colon cancer patients, showed a similar pattern of increase in claudin-1 and HDAC-2 mRNA expression throughout all stages of colon cancer. Inhibition of claudin-1 expression by HDAC-2-specific small interfering RNA further supported the role of HDAC-2 in this regulation. Taken together, we report a novel post-transcriptional regulation of claudin-1 expression in colon cancer cells and further show a functional correlation between claudin-1 expression and TSA-mediated regulation of invasion. As HDAC inhibitors are considered to be promising anticancer drugs, these new findings will have implications in both laboratory and clinical settings.

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“…The above are also supported by our experiments, which shows that DNA methyltransferase (DNMT1) inhibits the expression of CLDN6 to affect the function of tight junction in breast cancer MCF-7 cells in our unpublished work. In addition, it is reported that some TFBS, including those for AP-1, c-Jun, ATF-2, HNF-4α and COUP-TF have been shown to contribute to CLDN6 regulation ( 29 – 34 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis reveals potential properties of human Claudin-6 regulation and functions

Lin

Guo

et al. 2017

Oncology Reports

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Abstract. is an integral component of the tight junction proteins in polarized epithelial and endothelial cells and plays a crucial role in maintaining cell integrity. Deregulation of CLDN6 expression and distribution in tumor tissues have been widely documented and correlated with cancer progression and metastasis. However, a complete mechanistic understanding of CLDN6 regulation and function remains to be studied. Herein, we show new potential properties of CLDN6 regulation and functions from bioinformatics analysis. Using numerous algorithms to characterize the CLDN6 gene promoter elements and the CLDN6 protein structure, physio-chemical and localization properties, and its evolutionary relationships. CLDN6 is regulated by a diverse set of transcription factors (SP1, SPR, AML-1a, CdxA, CRE-BP and CREB) and associated with the levels of methylation of CpG islands in promoters. The structural properties of CLDN6 indicate that it promotes cancer cell behavior via the ASK1-p38/JNK MAPK secretory signaling pathway. In conclusion, this information from bioinformatics analysis will help future attempts to better understand CLDN6 regulation and functions.

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Prevention of murine experimental corneal trauma by epigenetic events regulating claudin 6 and claudin 9

Abstract: Epigenetic regulators enhance corneal barrier impairment by modulating TJs, so epigenetic regulation is a possible therapeutic method for corneal trauma.

Cited by 10 publications

References 44 publications

Trichostatin-A modulates claudin-1 mRNA stability through the modulation of Hu antigen R and tristetraprolin in colon cancer cells

Trichostatin-A modulates claudin-1 mRNA stability through the modulation of Hu antigen R and tristetraprolin in colon cancer cells

HDAC inhibitors regulate claudin-1 expression in colon cancer cells through modulation of mRNA stability

Bioinformatic analysis reveals potential properties of human Claudin-6 regulation and functions

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