Browse
Submit Data
Databases
API
Help
Login

Dataset Information

124 Views

1 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 38

Genes expression in xenografts obtained from 15 months cigarette smoke condensate (CSC)-exposed HBEC cells following expression of KRASV12

ABSTRACT: We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) for transformation by a single oncogene. The smoke-induced, chromatin changes include initial repressive polycomb marking of genes later manifesting abnormal DNA methylation by 10 months. At this time, cells manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation. Overall design: Gene expression in xenografts obtained from two biological replicates (rep 1 and rep2) of 15 months cigarette smoke condensate (CSC)-exposed HBEC cells following expression of KRASV12. Gene expression in Control cells at the same time point and expressing KRASV12 was used for comparison in final analysis.

INSTRUMENT(S): Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Feature Number version)

SUBMITTER: Hariharan Easwaran

PROVIDER: GSE101862 | GEO | 2017-10-21

SECONDARY ACCESSION(S): PRJNA395727

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

primary

			Action	DRS
	GSE101862_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 2 of 2

Similar Datasets

Methylation analysis of HBEC cells exposed to cigarette smoke condensate (CSC) over a period of 15 months

Project description:We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) for transformation by a single oncogene. The smoke-induced, chromatin changes include initial repressive polycomb marking of genes later manifesting abnormal DNA methylation by 10 months. At this time, cells manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation. Overall design: Bisulphite converted DNA from control and CSC treated cells from two biological replicates (rep 1 and rep2) over a period of 15 months. Additionally methylation analysis of 15 month Control and CSC cells from both replicates expressing empty vector (EV) or mutant KRAS (KRASV12) and tumor xenografts obtained from CSC cells with KRASV12 from both replicates. DNA was hybridised to the Illumina Infinium 450k Human Methylation Beadchip

2017-10-21 | GSE101673 | GEO

Gene Expression of HBEC-3KT cells exposed to cigarette smoke condensate (CSC) over a period of 15 months

Project description:We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) for transformation by a single oncogene. The smoke-induced, chromatin changes include initial repressive polycomb marking of genes later manifesting abnormal DNA methylation by 10 months. At this time, cells manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation. Overall design: Gene expression in CSC treated cells from two biological replicates (rep 1 and rep2) over a period of 15 months. Gene expression in Control and CSC treated at 15 months expressing empty vector (EV) or KRASV12. Data is represented as fold change in CSC treated cells over control (DMSO treated) cells.

2017-10-21 | GSE101863 | GEO

Exome-seq analysis of human bronchial epithelial cells (HBEC3KT) cells pre and post treatment with DMSO (Control) or 10 µg/ml cigarette smoke condensate (CSC) for 15 months and tumor xenografts obtained with 15 month CSC treated cells expressing KRASV12

Project description:We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) for transformation by a single oncogene. The smoke-induced, chromatin changes include initial repressive polycomb marking of genes later manifesting abnormal DNA methylation by 10 months. At this time, cells manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation. Overall design: HBEC cells treated with DMSO (Control) or 10 µg/ml CSC for 15 months. Xenografts were obtained by subcutaneously injecting 15 month CSC treated cells expressing KRASV12 in NSG mice.

2017-10-21 | GSE103150 | GEO

Chip-seq analysis of H3K4me3, H3K27me3, DNMT1 and EZH2 binding to chromatin following acute (10 days) and chronic (10 months) treatment of human bronchial epithelial cells (HBEC3KT) cells with 10 µg/ml cigarette smoke condensate (CSC).

Project description:We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) for transformation by a single oncogene. The smoke-induced, chromatin changes include initial repressive polycomb marking of genes later manifesting abnormal DNA methylation by 10 months. At this time, cells manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation. Overall design: HBEC cells treated with 10 µg/ml CSC for 10 months. Control (DMSO treated) and CSC treated cells were harvested at 10 days (acute exposure) and 10 months (chronic exposure) and processed for ChIP to examine genome wide enrichment of H3K4me3, H3k27me3 and binding of DNMT1 and EZH2. ChIPed DNA was analyzed by ChIP-seq.

2017-10-21 | GSE103331 | GEO

Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate.

Project description:Limited information is available regarding epigenomic events mediating initiation and progression of tobacco-induced lung cancers. In this study, we established an in vitro system to examine epigenomic effects of cigarette smoke in respiratory epithelia. Normal human small airway epithelial cells and cdk-4/hTERT-immortalized human bronchial epithelial cells (HBEC) were cultured in normal media with or without cigarette smoke condensate (CSC) for up to 9 months under potentially relevant exposure conditions. Western blot analysis showed that CSC mediated dose- and time-dependent diminution of H4K16Ac and H4K20Me3, while increasing relative levels of H3K27Me3; these histone alterations coincided with decreased DNA methyltransferase 1 (DNMT1) and increased DNMT3b expression. Pyrosequencing and quantitative RT-PCR experiments revealed time-dependent hypomethylation of D4Z4, NBL2, and LINE-1 repetitive DNA sequences; up-regulation of H19, IGF2, MAGE-A1, and MAGE-A3; activation of Wnt signaling; and hypermethylation of tumor suppressor genes such as RASSF1A and RAR-beta, which are frequently silenced in human lung cancers. Array-based DNA methylation profiling identified additional novel DNA methylation targets in soft-agar clones derived from CSC-exposed HBEC; a CSC gene expression signature was also identified in these cells. Progressive genomic hypomethylation and locoregional DNA hypermethylation induced by CSC coincided with a dramatic increase in soft-agar clonogenicity. Collectively, these data indicate that cigarette smoke induces 'cancer-associated' epigenomic alterations in cultured respiratory epithelia. This in vitro model may prove useful for delineating early epigenetic mechanisms regulating gene expression during pulmonary carcinogenesis.

2010-01-01 | S-EPMC6329296 | BioStudies

MicroRNA microarray between smoking-induced human bronchial epithelial cell (HBEC)-derived extracellular vesicles (EVs) and non-treated HBEC-derived Evs

Project description:To identify exosomal miRNAs that regulate smoking-induced lung myofibroblast differentiation, we conducted a miRNA microarray between smoking-induced HBEC-derived EVs and non-treated HBEC-derived EVs. Overall design: Cigarette smoke extract (CSE) was prepared for smoking exposure model in vitro. Forty milliliters of cigarette smoke was drawn into the syringe and slowly bubbled into sterile serum-free cell culture media in a 15-ml BD falcon tube. One cigarette was used for the preparation of 10 mL of solution. CSE solution was filtered (0.22 μm) to remove insoluble particles and was designated as a 100% CSE solution. We analyzed the role of CSE induced HBEC-derived EVs in the airway microenvironment. After HBECs were incubated in the non-FBS containing medium with or without a low-concentration CSE (1.0%) for 2 days, we collected conditioned medium (on day 4, 6) and isolated EVs by ultracentrifugation. After then, we collected exosomal RNA and analyzed exosomal microRNA microarray.

2018-02-19 | GSE66119 | GEO

PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis.

Project description:Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence. Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation. Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis. Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC). Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation. To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed. PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry. We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence. CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC. Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs. These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC. Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD.

2015-01-01 | S-EPMC4502689 | BioStudies

Chronic Cigarette Smoke-Induced Epigenomic Changes Precede Sensitization of Bronchial Epithelial Cells to Single-Step Transformation by KRAS Mutations.

Project description:We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adenosquamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation.

2017-01-01 | S-EPMC5596892 | BioStudies

Homo sapiens

Project description:Genes expression in xenografts obtained from 15 months cigarette smoke condensate (CSC)-exposed HBEC cells following expression of KRASV12

| PRJNA395727 | ENA

Cigarette smoke alters primary human bronchial epithelial cell differentiation at the air-liquid interface.

Project description:The differentiated human airway epithelium consists of different cell types forming a polarized and pseudostratified epithelium. This is dramatically altered in chronic obstructive pulmonary disease (COPD), characterized by basal and goblet cell hyperplasia, and squamous cell metaplasia. The effect of cigarette smoke on human bronchial epithelial cell (HBEC) differentiation remains to be elucidated. We analysed whether cigarette smoke extract (CSE) affected primary (p)HBEC differentiation and function. pHBEC were differentiated at the air-liquid interface (ALI) and differentiation was quantified after 7, 14, 21, or 28 days by assessing acetylated tubulin, CC10, or MUC5AC for ciliated, Clara, or goblet cells, respectively. Exposure of differentiating pHBEC to CSE impaired epithelial barrier formation, as assessed by resistance measurements (TEER). Importantly, CSE exposure significantly reduced the number of ciliated cells, while it increased the number of Clara and goblet cells. CSE-dependent cell number changes were reflected by a reduction of acetylated tubulin levels, an increased expression of the basal cell marker KRT14, and increased secretion of CC10, but not by changes in transcript levels of CC10, MUC5AC, or FOXJ1. Our data demonstrate that cigarette smoke specifically alters the cellular composition of the airway epithelium by affecting basal cell differentiation in a post-transcriptional manner.

1000-01-01 | S-EPMC4313097 | BioStudies

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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