Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers

ABSTRACT: Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69770 | GEO | 2018/02/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers

Project description:Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis

2018-02-07 | GSE94986 | GEO

Analysis of miRNA expression profiling in 3 samples(normal, cigarette smoking and lung cancer population's serum)

2014-06-17 | GSE58540 | GEO

Analysis of miRNA expression profiling in 3 samples(normal, cigarette smoking and lung cancer population's serum)

Project description:Using the highly sensitive miRNA array, we determined the serum miRNAs profiles of 10 non-smokers, 10 smokers and 10 lung cancer patients by miRCURY LNA™ microRNA Arrays. Differential expressed miRNAs were further validated in a larger scale samples. We found that let-7i-3p and miR-154-5p were significantly downregulation in serum of smokers and lung cancer patients. The serum level of let-7i-3p and miR-154-5p is associated with smoking and smoking-related lung cancer. In this study, we mix 10 samples with equal volume of each group(non-smoking control group,smoking group and lung cancer group ) and run RNA extractions. And then miRCURYTM LNA Array (v.16.0) was applied in the studying of miRNA expression profile and its alteration to gain the miRNA expression profile to compare the variety between each two groups respectively.

2014-06-17 | E-GEOD-58540 | biostudies-arrayexpress

DNA Methylation-dependent regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice.

Project description:Global DNA hypomethylation in CD4+ cells in SLE patients was suggested to play a key role in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Ctse, in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and mRNA upregulated in MRL compared with B6 mice. One of methyl-CpGs, mCGCG was hypomethylated and mutated to CGGG in MRL mice. Kaiso is known to bind mCGCG and we hypothesized that it represses expression of Ctse. The binding of Kaiso to mCGCG site in B6 was reduced in MRL mice revealed by ChIP-PCR. EL4 cells treated with 5-azaC and/or TSA showed the suppression of the binding of Kaiso to mCGCG motif and the overexpression of Ctse was demonstrated by qPCR. Ctse gene silencing by siRNA in EL4 cells resulted in reduction of IL-10 secretion. Accordingly, IL10 and CTSE mRNAs up-regulated in CD4+ T cells both in MRL mice and the patients with SLE. The hypomethylation of mCGCG motif, reduced recruitment of Kaiso, and increased expression of Ctse and Il-10 in CD4+ cells may be involved in the pathogenesis of SLE.

2017-08-13 | GSE102421 | GEO

Persistence of Smoking-induced Dysregulation of Small Airway Epithelium miRNA Expression Despite Smoking Cessation

Project description:Rationale: Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD) and lung cancer remains significantly higher compared to never-smokers. Objectives: Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE), we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. Methods: SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 10 healthy never-smokers and 10 healthy smokers, before and after they quit for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. Results: There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy never-smokers (p<0.01, fold-change >1.5), with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway the top enriched pathway of the target genes of the persistent deregulated miRNAs. Conclusions: In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammation diseases or lung cancer, it is likely that persistent smoking-related changes in small airway epithelium miRNAs play a role in the subsequent development of these disorders.

2015-11-23 | GSE53519 | GEO

DNA hydroxy-methylation data of tumor and non-tumor liver (NTL) tissues from Peruvian patients with hepatocellular carcinoma (HCC)

Project description:A large fraction of HCC in Peru arises in younger, non-cirrhotic patients. Global DNA hydroxy-methylation analysis of the HCC and NTL tissues demonstrate that hydroxy-methylation conversion interplays with gene expression to enact cell fate determination and cancer cell reprogramming. We used microarrays to identify hydroxy-methylated CpGs by comparison to Gene Expression Omnibus (GEO) series GSE136319 and GSE136380.

2021-01-31 | GSE136583 | GEO

GNPS Metabolomics Workbench ST001610 - GNPS Control (DMSO 0.1%; v/v) and 10 uM DRB18 treated A549 lung cancer cells in vitro for 48 hours

Project description:Control (DMSO 0.1%; v/v) and 10 M DRB18 were used to treated 5 million A549 lung cancer cells in vitro for 48 hours. The untargeted metabolomics analysis was performed on the cell lysates. The main objective of the study was to determine changes in metabolite abundances in lung cancer after treatment with DRB18, an inhibitor of glucose transporter proteins.

2021-02-15 | MSV000086879 | GNPS

RNA sequencing showing the different response pattern between lung epithelial cells and lung cancer cells after radiation

Project description:To seek if ionizing radiation have different biological effect on lung normal cells and cancer cells, we treated lung epithelial cell line BEAS-2B, non-small cell lung cancer cell line A549 and small cell lung cancer cell line H446 with 10 Gy X-ray radiation

2022-12-31 | GSE211118 | GEO

Genome-wide screening of transcriptional modulation in non-smoking female lung cancer in Taiwan

Project description:Although smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of cigarette smoking, extremely lower than those in Caucasian females. This report is a comprehensive analysis of the molecular signature of non-smoking female lung cancer in Taiwan.

2011-01-30 | GSE19804 | GEO

Smoking Status Impacts microRNA Mediated Prognosis and Lung Adenocarcinoma Biology

Project description:Cigarette smoke is associated with the majority of lung cancers: however, 25% of lung cancer patients are non-smokers, and half of all newly diagnosed lung cancer patients are former smokers. Lung tumors exhibit distinct epidemiological, clinical, pathological, and molecular features depending on smoking status, suggesting divergent mechanisms underlie tumorigenesis in smokers and non-smokers. MicroRNAs (miRNAs) are integral contributors to tumorigenesis and mediate biological responses to smoking. Based on the hypothesis that smoking-specific miRNA differences in lung adenocarcinomas reflect distinct tumorigenic processes selected by different smoking and non-smoking environments, we investigated the contribution of miRNA disruption to lung tumor biology and patient outcome in the context of smoking status. Results: We discovered novel and distinct smoking-status-specific patterns of miRNA and miRNA-mediated gene networks, and identified miRNAs that were prognostically significant in a smoking-dependent manner. Conclusions: We conclude that miRNAs disrupted in a smoking-status-dependent manner affect distinct cellular pathways and differentially influence lung cancer patient prognosis in current, former and never smokers. Our findings may represent promising biologically relevant markers for lung cancer prognosis or therapeutic intervention.

2014-10-30 | GSE62182 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data