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RESEARCH PRODUCT
Cigarette smoke affects the onco-suppressor DAB2IP expression in bronchial epithelial cells of COPD patients
Giulia AnzaloneRoberto MarcheseFabio Luigi Massimo RicciardoloGiuseppe ArcoleoAngela Marina MontalbanoMonica MoscatoGiusy Daniela AlbanoMirella ProfitaFabio BucchieriFabio BucchieriCaterina Di SanoRosalia Gagliardosubject
Jumonji Domain-Containing Histone DemethylasesLung NeoplasmsCigar SmokingCelllcsh:MedicineApoptosismacromolecular substancesArticlePulmonary Disease Chronic ObstructiveRisk FactorsmedicineHumansEnhancer of Zeste Homolog 2 ProteinNeoplasm Invasivenesslcsh:ScienceLung cancerA549 CellOncogenesisInflammationA549 cellRegulation of gene expressionCOPDMultidisciplinarybusiness.industrylcsh:REZH2ApoptosiJumonji Domain-Containing Histone DemethylaseCancerras GTPase-Activating Proteinmedicine.diseaseAlveolar Epithelial Cellrespiratory tract diseasesLung NeoplasmGene Expression Regulation NeoplasticNeoplasm Invasiveness Pulmonary Disease Chronic Obstructivemedicine.anatomical_structureA549 Cellsras GTPase-Activating ProteinsApoptosisAlveolar Epithelial CellsCancer researchlcsh:QbusinessHumanairway diseasedescription
AbstractCigarette smoke is a risk factor for COPD and lung cancer. In cancer, epigenetic modifications affect the expression of Enhancer of Zester Homolog 2 (EZH2), and silenced disabled homolog 2 interacting protein gene (DAB2IP) (onco-suppressor gene) by Histone H3 tri-methylation in lysine 27 (H3K27me3). In“ex vivo”studies, we assessed EZH2, H3K27me3 and DAB2IP immunoreactivity in bronchial epithelial cells from COPD patients (smokers, ex-smokers), Smoker and control subjects. In“in vitro” experiments we studied the effect of cigarette smoke extract (CSE) on EZH2/H3K27me3/DAB2IP expression, apoptosis, invasiveness, and vimentin expression in 16HBE, primary cells, and lung cancer cell lines (A549) long-term exposed to CSE. Finally, in “in vitro”studies, we tested the effect of GSK343 (selective inhibitor of EZH2). EZH2 and H3K27me3 expression was higher, while DAB2IP was lower levels, in bronchial epithelium from COPD and Smokers than in Controls. CSE increased EZH2, H3K27me3 expression and decreased DAB2IP, cell apoptosis and invasiveness in epithelial cells. GSK343 restored the effects of CSE. Cigarette smoke affects EZH2 expression, and reduced DAB2IP via H3K27me3 in COPD patients. The molecular mechanisms associated with EZH2 expression, generate a dysregulation of cell apoptosis, mesenchymal transition, and cell invasiveness in bronchial epithelial cells, encouraging the progression of airway inflammation toward lung cancer in COPD patients.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-10-01 |