ArticleAmerican journal of cancer research2013
Effect of epigenetic histone modifications on E-cadherin splicing and expression in lung cancer.
Article in American journal of cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Novel Histone Deacetylase 6 Inhibitor Confers Anti-inflammatory Effects and Enhances Gut Barrier Function.Gut and liver · 2023Article
- Recent advancement of HDAC inhibitors against breast cancer.Medical oncology (Northwood, London, England) · 2023Review
- HDAC2 Induces DNA Methyltransferase DNMT3B Expression to Regulate the Wnt Signaling Pathway and Thus Promotes Glioma Development and Progression.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- MicroRNA-3935 promotes human trophoblast cell epithelial-mesenchymal transition through tumor necrosis factor receptor-associated factor 6/regulator of G protein signaling 2 axis.Reproductive biology and endocrinology : RB&E · 2021Article
- Proteomic Analysis of Zeb1 Interactome in Breast Carcinoma Cells.Molecules (Basel, Switzerland) · 2021Article
- Characterization of Histone Deacetylase Mechanisms in Cancer Development.Frontiers in oncology · 2021Review
- Integrated Assessment of Viral Transcription, Antigen Presentation, and CD8Journal of virology · 2020Article
- The strong propensity of Cadherin-23 for aggregation inhibits cell migration.Molecular oncology · 2019Article
- The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome.Clinical & experimental metastasis · 2018Review
- Novel Polyamine-Naphthalene Diimide Conjugates Targeting Histone Deacetylases and DNA for Cancer Phenotype Reprogramming.ACS medicinal chemistry letters · 2017Article
- HDACs and HDAC Inhibitors in Cancer Development and Therapy.Cold Spring Harbor perspectives in medicine · 2016Review
- An epithelial marker promoter induction screen identifies histone deacetylase inhibitors to restore epithelial differentiation and abolishes anchorage independence growth in cancers.Cell death discovery · 2016Article
- A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition.Cell adhesion & migration · 2015Review
- Prediction of non-small cell lung cancer metastasis-associated microRNAs using bioinformatics.American journal of cancer research · 2015Article
- Transcription regulation of E-cadherin by zinc finger E-box binding homeobox proteins in solid tumors.BioMed research international · 2014Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We have identified an alternatively spliced, non-functional aberrant E-cadherin transcript that lacks exon 11 and is over expressed in malignant cells as compared to the normal non-malignant cells. This increase in the aberrant transcript is a mechanism of loss of E-cadherin gene expression as it is rapidly degraded by the nonsense mediated decay pathway. To study the mechanism of this gene missplicing we analyzed the role of histone epigenetic modifications in lung cancer cell lines. The treatment of low E-cadherin lung cancer cell lines with histone deacetylase inhibitor (HDACi, MS-275) resulted in the preferential expression of the correctly spliced transcripts in the low E-cadherin expressing cell lines only. Chromatin immunoprecipitation (ChIP) assays revealed that the histone hypoacetylation levels correlate with aberrant exon 11 splicing as there is more aberrant splicing in cell lines with E-cadherin promoter hypoacetylation. Inactivation of histone deacetylases (HDAC) 1, 2 and 3 resulted in an increase in E-cadherin expression and an increase in the ratio of the correctly spliced E-cadherin transcript. As transcription of the gene is closely linked to splicing, we considered the possibility that change in E-cadherin transcription correlates with splicing. The Zeb1 epithelial-mesenchymal transformation (EMT) inducer silences E-cadherin expression and could also alter the splicing of this exon. Inhibition of the E-cadherin promoter transcription with Zeb1 expression increases aberrant splicing and the reverse is observed when Zeb1 is knocked down. The role of HDAC inhibitors was also studied in vivo in a immunodeficient mouse xenograft model. Exposure of mice to HDACi resulted in growth inhibition, increase in E-cadherin expression, alteration of aberrant splicing and the reversal of EMT in mouse tumors. The findings support the modulation of E-cadherin exon 11 inclusion or exclusion by histone epigenetic modifications as they change the overall chromatin structure. The results provide an interesting link between epigenetic alterations in cancer cells and gene splicing in addition to their effect on gene silencing.
Indexed as
Identifiers
23977447PMC3744017W149284971What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.