Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA202232 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1029120.fastq.gz | Fastqsanger.gz | |||
| SRR1029130.fastq.gz | Fastqsanger.gz | |||
| SRR1029121.fastq.gz | Fastqsanger.gz | |||
| SRR1029131.fastq.gz | Fastqsanger.gz | |||
| SRR1029122.fastq.gz | Fastqsanger.gz |
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Project description:High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients. ChIP sequencing of active enhancer mark h3k27ac in colon epithelium from wild type mice and NAG-1 transgenic mice treated with either low-fat diet or high-fat diet. The gene expression component of the study is included in GSE46843.
2014-01-16 | E-GEOD-46748 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide. Obesity is a major risk factor with long-lasting effects on the predisposition to CRC even after weight loss; however, the mechanistic underpinnings remain poorly understood. Using a diet-induced obesity mouse model, we profiled cell-intrinsic alterations in colonic epithelium from young and aged obese mice compared with their age-matched controls, to gain insights into the progression of obesity-associated dysregulations in colonic cellular states. Cellular metabolic reprogramming occurred at early stage, boosting the number and function of stem/stem-like cells; while cell-intrinsic rewiring of signal transduction networks happened at later stage, promoting growth factor-independent proliferation. Strikingly, colonic DNA methylome was pre-programmed by obesity at young age priming for a tumor-prone gene signature after aging. Furthermore, obesity-related changes were substantially preserved after weight loss, potentially contributing to long-term predisposition to CRC. These findings broadened our perspectives on how obesity shapes the predisposition to CRC.
2017-12-19 | GSE100276 | GEO
Project description:High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon-specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients. We measured gene expression in colon epithelium from wild type mice and NAG-1 (non-steroidal anti-inflammatory drug (NSAID)-activated gene-1) transgenic mice fed either a 10% fat diet (LF) or a 60% fat diet (HF) for 20 weeks, using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol. The ChIP-seq component of the study is included in GSE46748.
2014-01-13 | E-GEOD-46843 | biostudies-arrayexpress
Project description:High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon-specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients.
2014-01-13 | GSE46843 | GEO
Project description:High-fat diet and obesity are high risk factors for colorectal cancer. The underlying mechanism is still unclear. Environmental factors alter the epigenome to affect gene expression thus the phenotype. In response to external stimuli, the cis-regulatory regions, especially enhancer loci, are key elements for regulating selective gene expression. We thus explored the effects of high-fat diet and the accompanying obesity on gene expression and the enhancer landscape in colon epithelium. High-fat diet exposed binding sites of transcription factors downstream of signaling pathways important in the initiation and progression of colon cancer. Meantime, colon specific enhancers were lost rendering the cells potential for dedifferentiation. The alteration at enhancer regions drives a specific transcription program promoting colon cancer progression. The comprehensive interrogation of enhancer changes by high-fat diet in colon epithelium provides a number of insights into the underlying biology of high-fat diet and obesity in increasing colon cancer risk, and provides potential therapeutic targets to treat obese colon cancer patients.
2014-01-16 | GSE46748 | GEO
Project description:Obesity is a worldwide epidemic associated with increased risk and progression of colon cancer. Here, we aimed to determine the role of adipose triglyceride lipase (ATGL), responsible for intracellular lipid droplet (LDs) utilization, in obesity driven colonic tumorigenesis. In local colon cancer patients, significantly increased ATGL levels in tumor tissue, compared to controls, were augmented in obese individuals. Elevated ATGL levels in human colon cancer cells (CCC) relative to non-transformed were augmented by an obesity mediator, oleic acid (OA). In CCC and colonospheres, enriched in colon cancer stem cells (CCSC), inhibition of ATGL prevented LDs utilization and inhibited OA-stimulated growth through retinoblastoma-mediated cell-cycle arrest. Further, transcriptomic analysis of CCC, with inhibited ATGL, revealed targeted pathways driving tumorigenesis and high-fat-diet obesity facilitated tumorigenic pathways. Inhibition of ATGL in colonospheres revealed targeted pathways in human colonic tumor crypt base cells (enriched in CCSC) derived from colon cancer patients. In CCC and colonospheres, we validated selected transcripts targeted by ATGL inhibition, some with emerging roles in colonic tumorigeneses (ATG2B, PCK2, PGAM1, SPTLC2, IGFBP1, ABCC3) and others with established roles (MYC, MUC2). These findings demonstrate obesity-promoted, ATGL-mediated colonic tumorigenesis and establishes therapeutic significance of ATGL in obesity reinforced colon cancer progression.
2022-02-05 | GSE195994 | GEO
Project description:Colorectal cancer is the third most common cancer. Obesity is a major risk factor with long-lasting effects on the predisposition to colorectal cancer; however, the mechanistic underpinnings remain poorly understood. To explore epigenetic mechanisms involved, we performed whole-genome bisulfite sequencing and RNA-Seq in colonic epithelium from control mice, obese mice, and formerly obese mice. We found that obesity-induced DNA methylation changes reprogrammed the transcriptome leading to a metabolic switch favoring long chain fatty acid oxidation, which is essential to colonic stem cell functions and colon tumorigenesis. Remarkably, persistent changes were observed after weight loss mainly at metabolic and cancer-related genes, underlying the long-term predisposition to colorectal cancer. In summary, we provide the epigenetic and metabolic basis of the link between obesity and colorectal cancer.
2017-12-19 | GSE85731 | GEO
Project description:Background & Aims: The obesity epidemic is associated with increased colon cancer progression. As lipid droplets (LDs) fuel tumor growth, we aim to determine the significance of diacyltransferases, DGAT1/2, responsible for LDs biogenesis, in obesity-mediated colonic tumorigenesis. Methods: Human colon cancer samples, colon cancer cells, colonospheres, and ApcMin/+ colon cancer mouse model on a high-fat diet were employed. For DGAT1/2 inhibition, enzymatic inhibitors and siRNA were used. Expression, pathways, cell cycle, and growth were assessed. Bioinformatic analysis of CUT&RUN and RNAseq data was performed. Results: DGAT1/2 levels in human colon cancer tissue are significantly elevated with disease severity and obesity (vs normal). Their levels are increased in human colon cancer cells (vs non-transformed) and further enhanced by fatty acids prevalent in obesity; augmented DGAT2 expression is MYC-dependent. Inhibition of DGAT1/2 improves FOXO3 activity by attenuating PI3K, resulting in reduced MYC-dependent DGAT2 expression and LDs accumulation, suggesting feedback. This inhibition attenuated growth in colon cancer cells and colonospheres via FOXO3/p27kip1 cell cycle arrest and reduced colonic tumors in ApcMin/+ mice on a high-fat diet. Transcriptomic analysis revealed that DGAT1/2 inhibition targeted metabolic and tumorigenic pathways in human colon cancer and colon cancer crypts, stratifying human colon cancer samples from normal. Further analysis revealed that this inhibition is predictive of advanced disease-free state and survival in colon cancer patients. Conclusion: This is a novel mechanism of DGAT1/2-dependent metabolic and tumorigenic remodeling in obesity-facilitated colon cancer, which provides a platform for the future development of effective treatments for colon cancer patients.
2024-10-14 | GSE278787 | GEO
Project description:Background & Aims: The obesity epidemic is associated with increased colon cancer progression. As lipid droplets (LDs) fuel tumor growth, we aim to determine the significance of diacyltransferases, DGAT1/2, responsible for LDs biogenesis, in obesity-mediated colonic tumorigenesis. Methods: Human colon cancer samples, colon cancer cells, colonospheres, and ApcMin/+ colon cancer mouse model on a high-fat diet were employed. For DGAT1/2 inhibition, enzymatic inhibitors and siRNA were used. Expression, pathways, cell cycle, and growth were assessed. Bioinformatic analysis of CUT&RUN and RNAseq data was performed. Results: DGAT1/2 levels in human colon cancer tissue are significantly elevated with disease severity and obesity (vs normal). Their levels are increased in human colon cancer cells (vs non-transformed) and further enhanced by fatty acids prevalent in obesity; augmented DGAT2 expression is MYC-dependent. Inhibition of DGAT1/2 improves FOXO3 activity by attenuating PI3K, resulting in reduced MYC-dependent DGAT2 expression and LDs accumulation, suggesting feedback. This inhibition attenuated growth in colon cancer cells and colonospheres via FOXO3/p27kip1 cell cycle arrest and reduced colonic tumors in ApcMin/+ mice on a high-fat diet. Transcriptomic analysis revealed that DGAT1/2 inhibition targeted metabolic and tumorigenic pathways in human colon cancer and colon cancer crypts, stratifying human colon cancer samples from normal. Further analysis revealed that this inhibition is predictive of advanced disease-free state and survival in colon cancer patients. Conclusion: This is a novel mechanism of DGAT1/2-dependent metabolic and tumorigenic remodeling in obesity-facilitated colon cancer, which provides a platform for the future development of effective treatments for colon cancer patients.
2024-10-14 | GSE278785 | GEO
Project description:Obesity, characterized by augmented inflammation and tumorigenesis, is linked to genetic predispositions, such as FOXO3 polymorphisms. As obesity is associated with aberrant macrophages infiltrating different tissue including the colon, we aimed to identify FOXO3-dependent transcriptomic changes in macrophages that drive obesity-mediated colonic inflammation and tumorigenesis. We found that in mouse colons, high-fat-diet-(HFD)-obesity led to diminished FOXO3 levels and increased macrophages. Transcriptomic analysis of mouse peritoneal FOXO3-deficient macrophages showed significant differentially expressed genes (DEGs; FDR<0.05) similar to HFD-obese colon. These DEGs related pathways, linked to mouse colonic inflammation and tumorigenesis, were similar to those in inflammatory bowel disease (IBD) and human colon cancer. Additionally, we identified a specific transcriptional signature for the macrophage-FOXO3 axis (MAC-FOXO382), which separated the transcriptome of affected tissue from control in both IBD (p=5.2E-08) and colon cancer (p=1.9E-11), revealing its significance in human colonic pathobiologies. Further, we identified (heatmap) and validated (qPCR) DEGs specific to FOXO3-deficient macrophages with established roles both in IBD and colon cancer (IL-1B, CXCR2, S100A8, S100A9, and TREM1) and those with unexamined roles in these colonic pathobiologies (STRA6, SERPINH1, LAMB1, NFE2L3, OLR1, DNAJC28 and VSIG10). These findings establish an important understanding of how HFD-obesity and related metabolites promote colonic pathobiologies.
2022-03-14 | GSE198058 | GEO