ArticleBMC cancer2013
E-cadherin gene re-expression in chronic lymphocytic leukemia cells by HDAC inhibitors.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06709885 (HDAC Inhibitor Combination With Immunochemotherapy in the Neoadjuvant Treatment of pMMR Locally Advanced Colon Cancer), which is not on this map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
HDAC Inhibitor Combination With Immunochemotherapy in the Neoadjuvant Treatment of pMMR Locally Advanced Colon Cancer: A Multicenter, Double-arm, Phase II Randomized Controlled Study
Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
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- Molecular Interactions Between Innate and Adaptive Immune Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications.Frontiers in immunology · 2018Review
- Influence of transcriptional variants on metastasis.RNA biology · 2018Review
- CDH1 Missense Variant c.1679C>G (p.T560R) Completely Disrupts Normal Splicing through Creation of a Novel 5' Splice Site.PloS one · 2016Article
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- Epigenetic roots of immunologic disease and new methods for examining chromatin regulatory pathways.Immunology and cell biology · 2015Review
- Histone deacetylases and mechanisms of regulation of gene expression.Critical reviews in oncogenesis · 2015Review
- Dynamic chromatin modification sustains epithelial-mesenchymal transition following inducible expression of Snail-1.Cell reports · 2013Article
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- Trichostatin A Restores Expression of Adherens and Tight Junction Proteins during Transforming Growth Factor β-Mediated Epithelial-to-Mesenchymal Transition.Journal of ophthalmic & vision researchArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe tumor suppressor gene E-cadherin gene is frequently silenced in chronic lymphocytic leukemia (CLL) cells and results in wnt-pathway activation. We analyzed the role of histone epigenetic modifications in E-cadherin gene silencing.
methodsCLL specimens were treated with histone deacetylase inhibitor (HDACi) MS-275 and analyzed for E-cadherin expression with western blot and RT-PCR analysis. The downstream effects of HDACi treated leukemic cells were studied by analyzing the effect on wnt-pathway signaling. HDACi induced alterations in E-cadherin splicing were investigated by transcript specific real time PCR analysis.
resultsTreatment of CLL specimens with histone deacetylase inhibitors (HDACi) treatment resulted in an increase of the E-cadherin RNA transcript (5 to 119 fold increase, n=10) in eight out of ten CLL specimens indicating that this gene is down regulated by histone hypoacetylation in a majority of CLL specimens. The E-cadherin re-expression in CLL specimens was noted by western blot analysis as well. Besides epigenetic silencing another mechanism of E-cadherin inactivation is aberrant exon 11 splicing resulting in an alternatively spliced transcript that lacks exon 11 and is degraded by the non-sense mediated decay (NMD) pathway. Our chromatin immunoprecipitation experiments show that HDACi increased the acetylation of histones H3 and H4 in the E-cadherin promoter region. This also affected the E-cadherin exon 11 splicing pattern as HDACi treated CLL specimens preferentially expressed the correctly spliced transcript and not the exon 11 skipped aberrant transcript. The re-expressed E- cadherin binds to β-catenin with inhibition of the active wnt-beta-catenin pathway in these cells. This resulted in a down regulation of two wnt target genes, LEF and cyclinD1 and the wnt pathway reporter.
conclusionThe E-cadherin gene is epigenetically modified and hypoacetylated in CLL leukemic cells. Treatment of CLL specimens with HDACi MS-275 activates transcription from this silent gene with expression of more correctly spliced E-cadherin transcripts as compared to the aberrant exon11 skipped transcripts that in turn inhibits the wnt signaling pathway. The data highlights the role of epigenetic modifications in altering gene splicing patterns.
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Registered trials
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