Genome-wide analysis of gene expression in partial Dnmt3a deleted colon mucosa cells of APC(Min/+) mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48115 | GEO | 2015/06/01
SECONDARY ACCESSION(S): PRJNA208946
REPOSITORIES: GEO
Similar Datasets
Project description:This experiment reports the RNA microarray data from the microarray analysis performed to the RNA isolated from colonic mucosal layer of Apc Min/+ mice. Apc Min/+ mice develop polyps in both the small and large intestine, with a greater incidence of intestinal adenomas observed in the former. We wanted to evaluate if maslinic acid (MA), a natural pentacyclic triterpene widely present in dietary plants and in olive fruit skins, could prevent spontaneous intestinal tumorigenesis in Apc Min/+ mice and through with mechanism MA executes its function. To do so, Apc Min/+ mice were fed for 6 weeks with a standard diet (control animals) or with the same diet supplemented with 100 mg of MA/kg feed (MA-treated animals). After 6 weeks, animals were killed and large intestine of each dead mouse was removed and placed on a plastic plate that was kept at 4ºC. After removal of the rectum, the colon was opened longitudinally with fine scissors, and mucus and feces were washed away. The colonic mucosal layer was incubated in Trizol for 3 min and scraped off of the muscle layer with the edge of a sterile glass slide. Cells were transferred into 800 microL trizol. Total RNA was isolated by using the Trizol method according to the manufacturer's protocol. Subsequently, it was purified by using the RNeasy Mini kit and digesting it with DNase I (Qiagen) according to the manufacturer's protocol. RNA pellets were resuspended in DEPC-treated, RNase-free water, and their purity and quantity were determined spectrophotometrically by using the NanoDrop ND-1000. RNA samples were considered suitable for further processing if their absorbance ratio 260/280 was higher than 1.9. Integrity was tested by using lab-on-a-chip technology on the BioAnalyzer 2100.
2015-10-31 | E-MTAB-4007 | biostudies-arrayexpress
Project description:To analyse roles of HAI-1/Spint1 in intestinal tumorigenesis, we examined the effect of intestine-specific deletion of Spint1 gene on Apc(Min/+) mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods. Mouse small intestine tumor tissue or background mucosa lacking macroscopically visible tumors were proceeded to RNA extraction and hybridization on microarrays (Affymetrix Mouse Genome 430 2.0 Array). Non-tumor or tumor intestinal mucosa tissues of Apc (Min/+)/Spint1 (flox/flox) mice and non-tumor or tumor intestinal mucosa tissues of Apc (Min/+)/Spint1 (flox/flox)/Vil-Cre mice were analysed. The experiment was repeated respectively.
2013-04-01 | E-GEOD-40856 | biostudies-arrayexpress
Project description:To analyse roles of HAI-1/Spint1 in intestinal tumorigenesis, we examined the effect of intestine-specific deletion of Spint1 gene on Apc(Min/+) mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods. Mouse small intestine tumor tissue or background mucosa lacking macroscopically visible tumors were proceeded to RNA extraction and hybridization on microarrays (Affymetrix Mouse Genome 430 2.0 Array).
2013-04-01 | GSE40856 | GEO
Project description:Aberrant DNA methylation is frequent in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are poorly understood. Ten-Eleven Translocation (TET) dioxygenases and Thymine DNA Glycosylase (TDG) mediate active DNA demethylation by generating and removing oxidized cytosine species. TET1 and TDG mutations, and altered levels of oxidized cytosines have been identified in human CRC. To investigate the TET-TDG demethylation axis in intestinal tumorigenesis, we generated ApcMin mice that are devoid of Tet1 and/or Tdg, and characterized the methylome and transcriptome of intestinal adenomas. There were increased numbers (>30) of adenomas in ApcMin mice expressing the dominant-negative TdgN151A allele, whereas Tet1-deficient and Tet1/Tdg-double heterozygous ApcMin adenomas were larger and displayed features of erosion and invasion. Methylome analysis revealed reduction in global DNA hypomethylation in colonic adenomas from Tet1- and Tdg-mutant ApcMin mice, and hypermethylation of CpG islands in Tet1-mutant ApcMin mice. In addition, RNA sequencing showed upregulation of inflammatory, immune and interferon response genes in Tet1- and Tdg-mutant colonic adenomas compared to control ApcMin adenomas. The corresponding 127-gene inflammatory signature separated human colonic adenocarcinomas in four groups, closely aligned with their microsatellite or chromosomal instability, and characterized by different levels of DNA methylation and DNMT1 expression that anti-correlated with TET1 expression. These findings demonstrate a novel mechanism of epigenetic regulation during intestinal tumorigenesis by which TET1-TDG-mediated DNA demethylation may decrease methylation levels and inflammatory/interferon/immune responses, and is linked to the type of genomic instability.
2024-07-01 | GSE179313 | GEO
Project description:EHF is essential for epidermal and colonic epithelial homeostasis and suppresses Apc-initiated colonic tumorigenesis
| PRJNA723372 | ENA
Project description:Aberrant DNA methylation is frequently observed in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are poorly understood. Ten-Eleven Translocation (TET) dioxygenases and Thymine DNA Glycosylase (TDG) are involved in active DNA demethylation by generating and removing novel oxidized cytosine species. TET1 and TDG mutations, and alterations of the levels of oxidized cytosines have been identified in human CRC. To clarify the biological significance of the TET-TDG demethylation axis in intestinal tumorigenesis, we generated ApcMin mice that are devoid of Tet1 and/or Tdg, and characterized the methylome and transcriptome of intestinal adenomas by DREAM and RNA sequencing, respectively. Tet1-deficient and Tet1/Tdg-double heterozygous ApcMin adenomas manifested increased adenoma size and features of erosion or invasion, whereas an increased number (>30) of adenomas was found in Tdg-mutant ApcMin mice. Methylome analysis revealed progressive loss of global DNA hypomethylation in colonic adenomas from Tet1- and Tdg-deficient ApcMin mice, and hypermethylation of CpG islands in Tet1-deficient ApcMin mice. In addition, RNA sequencing showed upregulation of genes in inflammatory, immune and interferon response in Tet1- and Tdg-mutant colonic adenomas compared to control ApcMin adenomas. The corresponding 135-gene inflammatory signature separated human colonic adenocarcinomas into four groups, closely aligned with their microsatellite or chromosomal instability profile, and characterized by different levels of DNA methylation and DNMT1 expression levels that anti-correlated with TET1 expression levels. These findings demonstrate a novel mechanism of epigenetic regulation during intestinal tumorigenesis by which TET1-TDG-mediated active DNA demethylation decreases not only methylation levels, but also inflammatory/interferon/immune response, which impinges on the intrinsic features of genomic instability of the tumors. This study establishes a novel link, via inflammatory response, between epigenomic and genomic instability.
2023-10-01 | GSE179526 | GEO
Project description:Chemoprevention is a pragmatic approach to reduce the risk of colorectal cancer, one of the leading causes of cancer-related death in western countries. In this regard, maslinic acid (MA), a pentacyclic triterpene extracted from wax-like coatings of olives, is known to inhibit proliferation and induce apoptosis in colon cancer cell lines without affecting normal intestinal cells. The present study evaluated the chemopreventive efficacy and associated mechanisms of maslinic acid treatment on spontaneous intestinal tumorigenesis in Apc(Min/+) mice. Twenty-two mice were randomized into 2 groups: control group and MA group, fed with a maslinic acid-supplemented diet for six weeks. MA treatment reduced total intestinal polyp formation by 45% (P<0.01). Putative molecular mechanisms associated with suppressing intestinal polyposis in Apc(Min/+) mice were investigated by comparing microarray expression profiles of MA-treated and control mice and by analyzing the serum metabolic profile using NMR techniques. The different expression phenotype induced by MA suggested that it exerts its chemopreventive action mainly by inhibiting cell-survival signaling and inflammation. These changes eventually induce G1-phase cell cycle arrest and apoptosis. Moreover, the metabolic changes induced by MA treatment were associated with a protective profile against intestinal tumorigenesis. These results show the efficacy and underlying mechanisms of MA against intestinal tumor development in the Apc(Min/+) mice model, suggesting its chemopreventive potential against colorectal cancer.
2017-02-09 | MTBLS240 | MetaboLights
Project description:Loss of the APC tumor suppressor in the intestinal epithelium initiates the majority of human colorectal adenocarcinomas. Constitutive β-catenin activation is thought to underlie tumorigenesis induced by loss of APC, however β-catenin activation alone does not recapitulate all APC-loss phenotypes, suggesting that additional pathways are required. We demonstrate that aberrant activation of the Msi1 RNA binding protein occurs upon APC loss and that constitutive Msi1 activation alone is sufficient to phenocopy APC loss in the intestinal epithelium. Msi1 elicits these effects through binding of mRNAs encoding pleiotropic tumor suppressors resulting in promiscuous activation of quiescent intestinal stem cells, proliferative expansion of the stem cell compartment, crypt fission, and blocked differentiation. Further, we find these phenotypes to be largely dependent on mTORC1 activity, and demonstrate that loss of Msi activity is sufficient to abrogate tumorigenesis in mouse and human systems. Our findings implicate Msi1 as a central coordinator of APC loss-induced intestinal stem cell transformation and adenocarcinoma progression. 2 wild-type, 2 transgenic samples
2015-10-22 | E-GEOD-54598 | biostudies-arrayexpress
Project description:Details of the series are available in the publication Cardoso J. et al., âChromosomal instability in MYH- and APC-mutant adenomatous polypsâ, Cancer Research, accepted for publication. Abstract of the publication: âThe vast majority of colorectal cancers display genetic instability, either in the chromosomal (CIN) or microsatellite (MIN) forms. While CIN tumors are per definition aneuploid, MIN colorectal cancers, caused by loss of mismatch repair function, are usually near-diploid. Recently, bi-allelic germline mutations in the MYH gene, were found to be responsible for MAP (MYH associated polyposis), an autosomal recessive predisposition to multiple colorectal polyps, often indistinguishable from the dominant FAP (familial adenomatous polyposis) syndrome caused by inherited APC mutations. Here, we analyzed MYH- and APC-mutant polyps by combining laser-capture microdissection, isothermal genomic DNA amplification, and array-CGH (comparative genomic hybridization). Smoothed quantile regression methods were applied to the MAP and FAP genomic profiles to discriminate chromosomes predominantly affected by gains and losses. Up to 80% of the MAP polyps showed aneuploid changes, which is significantly higher than the 60% found among FAP polyps. Both MAP and FAP adenomas were characterized by frequent losses at chromosome 1p, 17, 19 and 22, and gains affecting chromosome 7 and 13. The observation that aneuploidy is already detectable at early stages of MYH-driven tumorigenesis raises the possibility that CIN may contribute significantly to accelerated tumor progression, increased cancer risk, and poor prognosis in MAP.â Details of the series are available in the publication Cardoso J. et al., âChromosomal instability in MYH- and APC-mutant adenomatous polypsâ, Cancer Research, accepted for publication.
2010-06-30 | E-GEOD-3898 | biostudies-arrayexpress
Project description:The APC (Adenomatous Polyposis Coli) gene encodes a large multidomain protein that plays an integral role in the Wnt/beta-catenin signaling pathway. The loss-of-function mutation in APC is considered the earliest genetic alteration in the course of adenoma-carcinoma sequence of colorectal cancer progression, and the resulting constitutive activation of Wnt/beta-catenin signaling is required for the maintenance of advanced colorectal cancer. In order to identify genes affected by loss of Apc function, we performed transcription profiling of mouse small intestinal tissues comparing polyps with normal mucosa of Apc+/Delta716 mice. We isolated total RNA from intestinal polyps and normal intestinal mucosa from 3 individual Apc+/Delta716 mice. Total RNA samples were then employed to perform microarray analysis (Agilent Whole Mouse Genome Microarray Ver. 2.0, 4x44K).
2020-11-01 | E-MTAB-9187 | biostudies-arrayexpress