Global DNA Methylation Analysis Of Bronchial Epithelial Cells From Patients With Asthma, COPD With And Without Lung Cancer

Background: The morbidity and mortality associated with tobacco smoking is well established. Nicotine is the addictive component of tobacco. Nicotine, through the non-neuronal α7nicotinic receptor, induces cell proliferation, neo-angiogenesis, epithelial to mesenchymal transition, and inhibits drug-induced apoptosis. Objective: To understand the genetic, molecular and cellular biology of addiction, chronic obstructive pulmonary disease and lung cancer. Methods: The search for papers to be included in the review was performed during the months of July- September 2018 in the following databases: PubMed (http://www.ncbi.nlm.nih.gov), Scopus (http://www.scopus.com), EMBASE (http://www.elsevier.com/online-tools/embase), and ISI Web of Knowledge (http://apps.webofknowledge.com/). The following searching terms: “nicotine”, “nicotinic receptor”, and “addiction” or “COPD” or “lung cancer” were used. </P><P> Patents were retrieved in clinicaltrials.gov (https://clinicaltrials.gov/). All papers written in English were evaluated. The reference list of retrieved articles was also reviewed to identify other eligible studies that were not indexed by the above-mentioned databases. </P><P> New experimental data on the ability of nicotine to promote transformation of human bronchial epithelial cells, exposed for one hour to Benzo[a]pyrene-7,8-diol-9-10-epoxide, are reported. Results: Nicotinic receptors variants and nicotinic receptors upregulation are involved in addiction, chronic obstructive pulmonary disease and/or lung cancer. Nicotine through α7nicotinic receptor upregulation induces complete bronchial epithelial cells transformation. Conclusion: Genetic studies highlight the involvement of nicotinic receptors variants in addiction, chronic obstructive pulmonary disease and/or lung cancer. A future important step will be to translate these genetic findings to clinical practice. Interventions able to help smoking cessation in nicotine dependence subjects, under patent, are reported.

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The Effect of Choline on DNA Methylation in the Hippocampus of the Offspring of Gestational Diabetes Mellitus (GDM) Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzaa058_010 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1252-1252

Author(s):

Kaydine Edwards ◽

Xinyin Jiang ◽

Hunter Korsmo

Keyword(s):

Dna Methylation ◽

Group Versus ◽

Control Group ◽

Global Dna Methylation ◽

High Fat ◽

Methylation Analysis ◽

Feeding Condition ◽

Control Groups ◽

Funding Sources ◽

Dna Methylation Analysis

Abstract Objectives The objective of this project is to determine the effects of choline supplementation on DNA methylation in the hippocampus of the offspring from mouse dams with GDM. Methods In this study, female mice were divided into four groups: high fat (HF) feeding (to induce GDM), HF with choline supplementation, normal fat (NF) control and NF with choline supplementation. The experimental groups followed their diets and supplements for 4 weeks before timed mating and throughout gestation. Thereafter, they were fed the NF diet during lactation. After weaning, the offspring were fed the HF diet for 6 weeks before dissection. Brain hippocampus was then dissected for DNA extraction and global DNA methylation analysis. Results Global DNA methylation was increased in the NF choline supplemented group versus the NF control group (P = 0.056); however, there were no differences between the HF choline versus the HF or NF control groups (P = 0.992). Conclusions In summary, there was an interaction between maternal HF feeding and choline supplementation in influencing global DNA methylation. Maternal HF feeding eliminated the increase in offspring hippocampal DNA methylation by choline supplementation observed under the NF feeding condition. Funding Sources NIGMS.

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Cigarette smoke affects the onco-suppressor DAB2IP expression in bronchial epithelial cells of COPD patients

Scientific Reports ◽

10.1038/s41598-019-52179-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Giulia Anzalone ◽

Giuseppe Arcoleo ◽

Fabio Bucchieri ◽

Angela M. Montalbano ◽

Roberto Marchese ◽

...

Keyword(s):

Lung Cancer ◽

Epithelial Cells ◽

Cigarette Smoke ◽

Cell Apoptosis ◽

Molecular Mechanisms ◽

Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Mesenchymal Transition ◽

Copd Patients ◽

Ezh2 Expression

Abstract Cigarette 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.

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