Development of gene expression signatures in colon tissues from wildtype and CARD9 knockout tumor mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE111615 | GEO | 2019/12/05
REPOSITORIES: GEO
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Project description:It is crucial to decipher the host-microbiota interactions as they are involved in intestinal homeostasis and diseases. Caspase Recruitment Domain 9 (Card9) is an inflammatory bowel disease (IBD) susceptibility gene coding for an adapter protein for innate immunity toward many microorganisms. Card9 mediates colitis recovery via interleukin 22 pathway activation and Card9-/- mice have enhanced susceptibility to colitis. To reveal the mechanisms responsible of this defect in Card9-/-mice, we compared colon transcriptomics in WT and Card9-/- mice before and during DSS-induced colitis. Mice transcriptomes clusterized according to the genotype supporting a pattern clearly different in WT and Card9-/- mice. The number of up-regulated genes at day 7 was largely higher in Card9-/- compared to WT mice. Pathway analyses of the induced transcripts showed a dominance of immune-related pathway with a stronger signal in Card9-/- mice. Interestingly, NOD-like receptor signaling pathway, in which CARD9 is involved, was an exception with weaker activation in Card9-/- than in WT mice. During the recovery period at day 12, pathways involved in cell proliferation and replication were significantly activated in WT compared to Card9-/- mice confirming the healing defect in Card9-/- mice. For the induction of colitis, mice were given drinking water supplemented with 2% (w/v) Dextran sulphate sodium (DSS) for 7 days, then allowed to recover by drinking water alone for 5 additional days. 3 mice of each groups (WT and Card9-/-) were sacrified before DSS administration. 5 WT mice and 4 Card9-/- mice were sacrified 7 days after DSS administration and 5 mice of each group were sacrified at day 12.
2016-04-05 | E-GEOD-67577 | biostudies-arrayexpress
Project description:Development of gene expression signatures in colon tissues from wildtype and CARD9 knockout tumor mice
| PRJNA437570 | ENA
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are using transcriptome profiling (RNA-seq) to evaluate the effects of anti-S100a9 antibody on the global transcriptome of the colon tissues of the AOM/DSS mouse model (a model that mimics the human colitis-associated colon cancer development). Methods: 36 five-week-old male ICR mice were randomized divided into three groups: control (i.e. no AOM/DSS and antibody treatment), AOM/DSS+IgG Ab (1.5 mg/kg), and AOM/DSS+anti-S100a9 Ab (1.5 mg/kg). Mice were intraperitoneal injected with a single dose of 10 mg/kg azoxymethane (AOM) (A5486; Sigma) on day 1. One week after the AOM injection, mice were given three cycles of DSS (cycle 1: 2%, 7 days; cycle 2: 1.5%, 5 days; and cycle 3: 1.5%, 5 days, DSS: 36–50 kDa; MP Biomedicals, CA, USA) in their drinking water, and then distilled water until the end of the experiment. Antibodies were administrated intravenously every two days during the three cycles of DSS treatment. Mice were sequentially killed randomly at the end of the 18th week, and at least five mice were killed for each group at each time point. RNAs were extracted by Trizol and sequenced by Solexa high-throughput sequencing service (Oebiotech, Shanghai, China). Data were extracted and normalized according to the manufacturer’s standard protocol.Each group has three mices' colon tissues be tested. Results: Log-fold changes of up- or down-regulated mRNAs between the control and experiment group were selected with a significance threshold of p<0.05. There are 1017 mRNAs were up-regulated and 815 were down-regulated in “AOM/DSS+IgG Ab" group comparing to “control" group. There are 385 mRNAs were up-regulated and 163 were down-regulated in “AOM/DSS+anti-S100a9 Ab" group comparing to “control" group. There are 1314 mRNAs were up-regulated and 968 were down-regulated in “AOM/DSS+anti-S100a9 Ab" group comparing to “AOM/DSS+IgG Ab". Conclusions: Our study describes the global transciptome changes of colon tissues of the AOM/DSS mouse model induced by anti-S100a9 antibody treatment.
2018-02-22 | GSE104614 | GEO
Project description:To find out which miRNAs are significantly differential expression and potentially involved in the process of inflammation promoting carcinogenesis of colorectal cancer (CRC). We established a colitis-associated CRC (AOM/DSS, Azoxymethane/Dextran sulfate sodium salt) model, colitis (DSS) model and high dose carcinogen (AOM, about 5 times AOM amount given than AOM/DSS model) model. At day 100 when tumor formed in AOM/DSS bearing mice (colitis-associated CRC mice) but no tumor was found in AOM (high dose carcinogen) and DSS model, we employed miRNA microarray as a discovery platform to identify genes with the potential to involve in the progression of CRC promoted by inflammation. 5-7 weeks female BALB/c mice, (1) AOM/DSS group: AOM 12.5mg/kg i.p. at day 1, DSS drinking 5d/21dx3circles from day 5; (2) AOM group: AOM 10mg/kg i.p. 1/weekx6 from day 1; (3) DSS group: DSS drinking 5d/21dx3circles from day 5. The distal colon epithelial tissues were collected at day100 when tumor formed in AOM/DSS bearing mice. The miRNA microarray experiments were performed together.
2013-05-10 | E-GEOD-44983 | biostudies-arrayexpress
Project description:Label-free proteomics from colon tumors induced in C57BL/6J mice following exposure to azoxymethane plus dextran sodium sulfate. Normal colon was taken from age matched mice not exposed to AOM/DSS.
2024-06-03 | PXD042677 | JPOST Repository
Project description:To find out which mRNAs are significantly differential expression and potentially involved in the process of inflammation promoting carcinogenesis of colorectal cancer (CRC). We established a colitis-associated CRC (AOM/DSS, Azoxymethane/Dextran sulfate sodium salt) model, colitis (DSS) model and high dose carcinogen (AOM, about 5 times AOM amount given than AOM/DSS model) model. At day 100 when tumor formed in AOM/DSS bearing mice (colitis-associated CRC mice) but no tumor was found in AOM (high dose carcinogen) and DSS model, we employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to involve in the progression of CRC promoted by inflammation. 5-7 weeks female BALB/c mice, (1) AOM/DSS group: AOM 12.5mg/kg i.p. at day 1, DSS drinking 5d/21dx3circles from day 5; (2) AOM group: AOM 10mg/kg i.p. 1/weekx6 from day 1; (3) DSS group: DSS drinking 5d/21dx3circles from day 5. The distal colon epithelial tissues were collected at day100 when tumor formed in AOM/DSS bearing mice. The whole genome microarray expression profiling experiments were performed together.
2013-05-10 | E-GEOD-44904 | biostudies-arrayexpress
Project description:It is crucial to decipher the host-microbiota interactions as they are involved in intestinal homeostasis and diseases. Caspase Recruitment Domain 9 (Card9) is an inflammatory bowel disease (IBD) susceptibility gene coding for an adapter protein for innate immunity toward many microorganisms. Card9 mediates colitis recovery via interleukin 22 pathway activation and Card9-/- mice have enhanced susceptibility to colitis. To reveal the mechanisms responsible of this defect in Card9-/-mice, we compared colon transcriptomics in WT and Card9-/- mice before and during DSS-induced colitis. Mice transcriptomes clusterized according to the genotype supporting a pattern clearly different in WT and Card9-/- mice. The number of up-regulated genes at day 7 was largely higher in Card9-/- compared to WT mice. Pathway analyses of the induced transcripts showed a dominance of immune-related pathway with a stronger signal in Card9-/- mice. Interestingly, NOD-like receptor signaling pathway, in which CARD9 is involved, was an exception with weaker activation in Card9-/- than in WT mice. During the recovery period at day 12, pathways involved in cell proliferation and replication were significantly activated in WT compared to Card9-/- mice confirming the healing defect in Card9-/- mice. Results published in Nature Medicine, doi:10.1038/nm.4102
2016-04-05 | GSE67577 | GEO
Project description:Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms play an important role in the initiation and progression of colon cancer. Curcumin is a dietary cancer preventive phytochemical with promising effect in suppressing colitis-associated colon cancer (CAC) in azoxymethane (AOM) and dextran sulfate sodium (DSS) mouse model. In the present study, we confirmed the effect of curcumin in suppressing colon cancer. Using Agilent SureSelect Methyl-seq and RNA-seq, we obtained single-base methylation profile and transcriptome analyses of epithelial cells from control group, AOM and DSS induced group (AOM+DSS), and AOM and DSS induced plus curcumin treated group (AOM+DSS+Curcumin) in a 18 weeks long-term colon cancer mouse model. The average DNA methylation levels of the three groups are significantly different also. Based on differential methylation patterns of three groups, several pathways of genes were identified including IL-8 signaling, LPS-stimulated MAPK signaling and colorectal cancer metastasis signaling. Among these methylated pathways and genes, Tnf, an inflammatory gene stood out with decreased DNA CpG methylation in the AOM-DSS as compared to the control group and interestingly curcumin reversed the CpG methylation (validated by pyrosequencing). The functional role of DNA methylation of Tnf was confirmed by in vitro luciferase transcriptional activity assay. In addition, we found that a group of genes associated with the inflammatory responses and their methylation level was decreased in AOM+DSS group but restored in the curcumin treated group. Taken together, in this study, aberrant DNA CpG methylation of the inflammatory response was found in colitis-associated colon cancer and curcumin restored their CpG methlyation, which could potentially explain the inflammatory and cancer protective effects of curcumin. (Note this GEO/dataset is the DNA methyl-seq part of the study.)
2018-06-11 | GSE102645 | GEO
Project description:Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms play an important role in the initiation and progression of colon cancer. Curcumin is a dietary cancer preventive phytochemical with promising effect in suppressing colitis-associated colon cancer (CAC) in azoxymethane (AOM) and dextran sulfate sodium (DSS) mouse model. In the present study, we confirmed the effect of curcumin in suppressing colon cancer. Using Agilent SureSelect Methyl-seq and RNA-seq, we obtained single-base methylation profile and transcriptome analyses of epithelial cells from control group, AOM and DSS induced group (AOM+DSS), and AOM and DSS induced plus curcumin treated group (AOM+DSS+Curcumin) in a 18 weeks long-term colon cancer mouse model. We observed differentially expressed genes in pair-wise comparison and identified several pathways of small set of genes involved in the potential preventive effect of curcumin. These pathways include LPS/IL-1 mediated inhibition of RXR function, NRF2-mediated oxidative stress response, aldosterone signaling in epithelial cells, production of NO and ROS in macrophages, and IL-6 signaling. The average DNA methylation levels of the three groups are significantly different also. Based on differential methylation patterns of three groups, several pathways of genes were identified including IL-8 signaling, LPS-stimulated MAPK signaling and colorectal cancer metastasis signaling. Among these methylated pathways and genes, Tnf, an inflammatory gene stood out with decreased DNA CpG methylation in the AOM-DSS as compared to the control group and interestingly curcumin reversed the CpG methylation (validated by pyrosequencing). These observations correlated with decreased, and increased with curcumin, Tnf expression in RNA-seq (validated by qPCR), respectively. The functional role of DNA methylation of Tnf was confirmed by in vitro luciferase transcriptional activity assay. In addition, we found that a group of genes associated with the inflammatory responses and their methylation level was decreased in AOM+DSS group but restored in the curcumin treated group. Taken together, in this study, aberrant DNA CpG methylation of the inflammatory response was found in colitis-associated colon cancer and curcumin restored their CpG methlyation, which could potentially explain the inflammatory and cancer protective effects of curcumin. (Note this GEO/dataset is the RNA-seq part of the study.)
2018-06-11 | GSE102342 | GEO
Project description:In humans with UC, low-grade dysplasia also develops predominantly in the distal colon, progresses more rapidly to neoplasia than proximal colon low-grade dysplasia and associates with worse patient prognosis. In a mouse model of colitis-associated carcinogenesis induced by administration of the mutagen AOM and the luminal toxin DSS, tumors also develop exclusively in the distal part of the large intestine. We monitored global changes in the transcriptome of mouse proximal and distal colon during exposure to AOM/DSS with the aim to define biological pathways and processes that characterize regional responses of the large intestine to colitis-associated carcinogenesis.
2015-06-01 | GSE64658 | GEO