Single-cell deconvolution of colon organoids exposed to carcinogens reveals novel insights into the early molecular events defining the role of smoking in colorectal cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA730892 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14580000_1.fastq.gz | Fastqsanger.gz | |||
| SRR14580000_2.fastq.gz | Fastqsanger.gz | |||
| SRR14580001_1.fastq.gz | Fastqsanger.gz | |||
| SRR14580001_2.fastq.gz | Fastqsanger.gz | |||
| SRR14580002_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 148 |
Similar Datasets
Project description:Even though smoking is associated with lung cancer, the exact molecular pathways that link carcinogens with inflammation and oncogenic transformation are not well elucidated. Nicotine-derived nitrosamine ketone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and Benzo(α)pyrene (BaP) are two major carcinogens in cigarette smoke and have not been tested in models that mimic inhaled exposure for prolonged periods of time. We treated ICR mice with intratracheal delivery of NNK and BaP three times a week for 18 months to mimic chronic smoking exposure. Mice developed epithelial dysplasia followed by lung cancers at increased rates relative to controls. Histology revealed myeloid inflammation in murine lung tissues. Exposure of lung epithelial cells to cigarette smoking condensate led to increased production of pro-inflammatory IL-1. Downstream mediator of IL-1β signaling, Interleukin 1 receptor associated kinase–4 (IRAK4), was overexpressed in murine lung tissues exposed to carcinogens in vivo. Two-thirds of human lung cancer samples also exhibited overactivated IRAK4 expression. IRAK4 was found to localize in microtubules in lung cancer cell lines. Using mass spectrometry on isolated microtubules, we observed that IRAK4 inhibition was associated with decreased phosphorylation of tubular motility proteins including MYH9. Inhibition of IRAK4 resulted in decreased invasion in lung cancer cell lines and reduced growth of lung cancer xenografts. These data demonstrate that smoking associated carcinogens cause myeloid inflammation that can be linked to oncogenic transformation via IRAK4 activation.
2024-10-23 | PXD053181 | Pride
Project description:Here, we used bulk RNA-seq data derived from healthy colon organoids (un)exposed to carcinogen. Through the use of external single cell RNA-seq data, we estimate changes in cell composition. We extend this analysis by controlling for cell composition and performing WGCNA to identify modules of co-expression differentially affected by carcinogen treatment in colon organoids.
2021-09-22 | GSE174650 | GEO
Project description:Genetic Architecture of Smoking and Smoking Cessation
| PRJNA75689 | ENA
Project description:Cigarette smoking accounts for approximately one in five deaths in the United States. Previous genomic studies have primarily focused on gene level differential expression to identify related molecular signatures and pathways, but the genome-wide effects of smoking on alternative isoform regulation and posttranscriptional modulation have not yet been described. We attempted to fill this void by identifying smoking-associated isoform switches and their responsible splicing events and consequences using RNA-seq.
2021-12-01 | GSE171730 | GEO
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
Project description:Deep sequencing of transcriptomes allows quantitative and qualitative analysis of many RNA species in a sample, with parallel comparison of expression levels, splicing variants, natural antisense transcripts, RNA editing and transcriptional start and stop sites the ideal goal. By computational modeling, we show how libraries of multiple insert sizes combined with strand-specific, paired-end (SS-PE) sequencing can increase the information gained on alternative splicing, especially in higher eukaryotes. Despite the benefits of gaining SS-PE data with paired ends of varying distance, the standard Illumina protocol allows only non-strand-specific, paired-end sequencing with a single insert size. Here, we modify the Illumina RNA ligation protocol to allow SS-PE sequencing by using a custom pre-adenylated 3M-bM-^@M-^Y adaptor. We generate parallel libraries with differing insert sizes to aid deconvolution of alternative splicing events and to characterize the extent and distribution of natural antisense transcription in C. elegans. Despite stringent requirements for detection of alternative splicing, our data increases the number of intron retention and exon skipping events annotated in the Wormbase genome annotations by 127 % and 121 %, respectively. We show that parallel libraries with a range of insert sizes increase transcriptomic information gained by sequencing and that by current established benchmarks our protocol gives competitive results with respect to library quality. Sequencing of mRNA from C. elegans with libraries of four differing insert sizes
2012-08-31 | E-GEOD-40507 | biostudies-arrayexpress
Project description:B cells were found to be directly associated with the onset and development of many smoking-induced diseases. However, the in vivo molecular response of B cells underlying the female cigarette smoking remains unknown. Using the genome-wide Affymetrix HG-133A GeneChip® microarray, we compared the gene expression profiles of peripheral circulating B cells between 39 smoking and 40 non-smoking healthy US white females.
2009-12-25 | GSE18723 | GEO
Project description:Smoking is a major risk factor for Urothelial carcinoma (UC). However the complex mechanisms, how smoking promotes carcinogenesis and tumour progression, remain obscure. A microarray based approached was therefore performed to detect the smoking derived gene expression alteration in non-malignant and malignant urothelial tissues from patients with superficial or invasive UC. Smoking enhanced cell migration and response to tissue damages. In non-malignant tissues smoking induced immune response and altered the cytoskeleton. In urothelial carcinoma, smoking altered extracellular and chromosome structures. Smoking affected tissues from patients with invasive carcinomamore strongly, up-regulating particularly growth factors and oncogenes in non-malignant tissue of patients with invasive but not with superficial carcinoma. In former smokers, comparable changes were seen in tissues form patients with invasive disease while they were minor or reversed in tissue of patients with superficial disease. Best but not complete tissue repair was suggestedfor non-malignant tissue from patients with superficial tumours. we used microarray techniques to define gene expression profile which may explain the contribution of smoking to urothelial carcinoma.
2013-03-20 | GSE21142 | GEO
Project description:Background: Epigenetics is involved in various human diseases. Smoking is one of the most common environmental factors causing epigenetic changes. The DNA methylation changes and mechanisms after quitting smoking have not yet been defined. The present study examined the changes in DNA methylation level before and after short-term smoking cessation and explored the potential mechanism. Methods: Whole blood and clinical data were collected in 8 patients before and after short-term smoking cessation, DNA methylation was assessed, and differentially methylated sites were analyzed, followed by a comprehensive analysis of the differentially methylated sites with clinical data. GO/KEGG enrichment and protein-protein interaction (PPI) network identified the hub genes. The differentially methylated sites were detected by GEO2R between former smoking and current smoking in GSE50660 from the GEO database. Then, a Venn analysis was carried out using the differentially methylated sites. GO/KEGG enrichment analysis was performed on the genes corresponding to the common DNA methylation sites, the PPI network was constructed, and hub genes were predicted. The enriched genes associated with the cell cycle were selected, and the gene expression was analyzed in pan-cancer based on the TCGA database. Results: Most of the DNA methylation levels were decreased after short-term smoking cessation; a total of 694 hypermethylated CPG sites and 3184 hypomethylated CPG sites were identified. The DNA methylation levels altered according to the clinical data (body weight, expiratory, and tobacco dependence score). Enrichment analysis, construction of PPI network, and pan-cancer analysis suggested that smoking cessation may be involved in various biological processes. Conclusions: Smoking cessation leads to epigenetic changes, mainly observed in the decline of most DNA methylation levels. Bioinformatics further identified the biologically relevant changes after short-term smoking cessation.
2023-08-08 | GSE201532 | GEO