Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice
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ABSTRACT:
PROVIDER: PRJNA692624 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13449164_1.fastq.gz | Fastqsanger.gz | |||
| SRR13449164_2.fastq.gz | Fastqsanger.gz | |||
| SRR13449165_1.fastq.gz | Fastqsanger.gz | |||
| SRR13449165_2.fastq.gz | Fastqsanger.gz | |||
| SRR13449166_1.fastq.gz | Fastqsanger.gz |
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Project description:The nuclear phosphatase mitogen-activate protein kinase phosphatase-1 (MKP-1) is a key negative regulator of the innate immune response through the regulation of the biosynthesis of proinflammatory cytokines. In colorectal cancer (CRC), which is induced mainly by chronic inflammation, Mkp-1 overexpression was found in addition to disturbances in Mkp-1 functions, which may play a role in cancer development in different types of tumors. However, the potential molecular mechanisms by which Mkp-1 influences CRC development is not clear. Here, we performed global gene expression profiling of Mkp-1 KO mice using RNA sequencing (RNA-seq) to explore the role of Mkp-1 in CRC progression using transcriptome analysis.
2021-01-17 | GSE164960 | GEO
Project description:BackgroundThe nuclear phosphatase mitogen-activate protein kinase phosphatase-1 (MKP-1) is a key negative regulator of the innate immune response through the regulation of the biosynthesis of proinflammatory cytokines. In colorectal cancer (CRC), which is induced mainly by chronic inflammation, Mkp-1 overexpression was found in addition to disturbances in Mkp-1 functions, which may play a role in cancer development in different types of tumors. However, the potential molecular mechanisms by which Mkp-1 influences CRC development is not clear. Here, we performed global gene expression profiling of Mkp-1 KO mice using RNA sequencing (RNA-seq) to explore the role of Mkp-1 in CRC progression using transcriptome analysis.MethodsAzoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were used to examine the most dramatic molecular and signaling changes that occur during different phases of CRC development in wild-type mice and Mkp-1 KO mice. Comprehensive bioinformatics analyses were used to elucidate the molecular processes regulated by Mkp-1. Differentially expressed genes (DEGs) were identified and functionally analyzed by Gene Ontology (GO), Kyoto Enrichment of Genes and Genomes (KEGG). Then, protein-protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software.ResultsPersistent DEGs were different in adenoma and carcinoma stage (238 & 251, respectively) and in WT and MKp-1 KO mice (221& 196, respectively). Mkp-1 KO modulated key molecular processes typically activated in cancer, in particular, cell adhesion, ion transport, extracellular matrix organization, response to drug, response to hypoxia, and response to toxic substance. It was obvious that these pathways are closely associated with cancer development and metastasis. From the PPI network analyses, nine hub genes associated with CRC were identified.ConclusionThese findings suggest that MKp-1 and its hub genes may play a critical role in cancer development, prognosis, and determining treatment outcomes. We provide clues to build a potential link between Mkp-1 and colitis-associated tumorigenesis and identify areas requiring further investigation.
| S-EPMC8152130 | biostudies-literature
Project description:Prenatal dexamethasone exposure (PDE) has long-term consequences in bone development. we investigated how PDE exerts persistent effect on bone metabolism in mouse offspring. Our results showed that PDE offspring exhibited reduced bone mass, fewer osteoblasts and diminished osteoprogenitors proliferation.And PDE increased MKP-1 expression, while decreasing H3 lysine 9 dimethylation (H3K9me2) at Mkp-1 gene locus. Mechanistically, dexamethasone suppressed osteoprogenitors proliferation by upregulating MKP-1 expression, notably through the inhibition of H3K9me2 modifications, which promoted demethylation and transcriptional activation of the Mkp-1 gene. Importantly, restoring histone methylation balance with PFI-90 treatment blocked the inhibitory effects of PDE on MAPK signaling in osteoprogenitors, and mitigated the detrimental impact of PDE on osteoprogenitor proliferation and bone development in the offspring. Therefore,we performed ChIP-seq for H3K9me2 to identify its role in related epigenetic changes.
2024-11-06 | GSE276769 | GEO
Project description:Previously, I have found that Mkp-1 knockout exacerbates inflammation, perturbs lipid metabolism, increases organ damage, mortality, and bacterial burdens. To understand the role of Mkp-1 in the regulation of host defense, we performed RNA-seq analysis using total RNA isolated from livers of uninfected and E. coli-infected wildtype and Mkp-1 knockout mice. Specifically, Mkp-1 wildtype and knockout (both on the C57/129 background) mice were infected with E. coli (O55:B5, ATCC 12014) at a dose of 2.5×107 CFU/g of body weight i.v., or given same volume of PBS. Mice were sacrificed 24 h post-infection to harvest organs. Livers were frozen clamping in liquid nitrogen, and stored at -80°C . Total RNA was isolated with Trizol and used for RNA-seq. RNA-seq results indicate that both E. coli infection and Mkp-1 knockout caused profound changes in the transcriptomes in the mouse livers.
2019-10-01 | GSE122741 | GEO
Project description:To shed lights on the potential candidate genes and molecular pathways in vitiligo pathomechanism and therapeutics, we compared the transcriptomes between depigmented and normal skin in Ets-1 knockout mice that spontaneously exhibit human vitiligo-like depigmentation. We performed gene expression profiling analysis using data obtained from RNA-seq of 1 depigmented and 1 pigmented skins of Ets-1 KO mice, and 1 normal skins of wild-type mice.
2023-04-15 | E-MTAB-12835 | biostudies-arrayexpress
Project description:To uncover molecular mechanisms specifically involved in the pathogenesis of colitis-associated colon cancer (CAC), we studied tumorigenesis in experimental models of CAC and sporadic CRC that mimic characteristics of human CRC. Using comparative whole genome expression profiling, we observed differential expression of epiregulin (Ereg) in mouse models of colitis-associated, but not sporadic colorectal cancer. Similarly, highly significant upregulation of Ereg expression was found in cohorts of patients with colitis-associated cancer in inflammatory bowel disease but not in sporadic colorectal cancer. Furthermore, tumor-associated fibroblasts were identified as major source of Ereg in colitis-associated neoplasias. Functional studies showed that Ereg-deficient mice, although more prone to colitis, are strongly protected from colitis-associated tumors, and data from serial endoscopic studies revealed that Ereg promotes growth rather than initiation of tumors. 4 samples of individual distal colitis-associated tumors (CAC) from 4 mice, 2 samples of tumor-free distal colon epithelium with a pool of 5 mice per sample (CAC contr), 5 samples of individual Apcmin/+ tumors from the distal colorectum of 5 mice (sporCRC) and 3 samples of tumor-free distal colon epithelium (pool of 4 mice per sample) (sporCRC contr). Colitis-associated tumorigenesis was performed by intraperitoneal injection of Azoxymethane (10mg/kg) (Sigma) into C57BL/6J wildtype mice followed by 3 cycles of Dextran Sodium Sulfate (DSS) in drinking water. Each DSS-cycle was composed of DSS (2.5% (w/v) (MP Biomedicals) in drinking water for 7 days, followed by a recovery phase with regular drinking water for 14 days. Sporadic tumors were from C57BL/6J-ApcMin/+/J mice. All tumors were obtained from the from the lower 6th of the large intestine and they had the same size covering between ¼ and up to ½ of the colonic circumferenc as evaluated by mini-endoscopy.
2013-04-01 | E-GEOD-43338 | biostudies-arrayexpress
Project description:Age-associated hematopoietic stem cell (HSC) dysfunction is accompanied by dramatic transcription changes, but it remains unclear whether specific transcripts could orchestrate these HSC aging phenotypes. Here, we performed epigenetic profiling in male mice to investigate the regulatory mechanisms underlying the HSC aging transcriptome and screen for potential aging driver genes. We show dysregulated 3D chromatin organization, altered histone modifications and changed chromatin accessibility shape the HSC aging transcriptome. From the compilation of these data, we identified a new looping structure formed between part of the Btaf1 gene and the whole Ide gene in old HSCs (OHSCs) which is accompanied by overexpression of a novel, shorter variant of Btaf1 (nBtaf1). Mechanistically, elevated expression of nBtaf1 drives the aging-associated overexpression of HSC- and megakaryocyte progenitor (MkP)-related genes by regulating TBP binding at their promoters which contributes to HSC expansion and elevated MkP production in aged mice. ShRNA mediated knockdown of nBtaf1 restores a younger HSC transcriptome and specifically represses aging-associated HSC expansion and elevated MkP production. In summary, our data provide high resolution analysis of a dysregulated HSC aging epigenome and reveal a novel Btaf1 variant that drives HSC aging phenotypes in mice.
2026-02-19 | GSE204933 | GEO
Project description:To uncover molecular mechanisms specifically involved in the pathogenesis of colitis-associated colon cancer (CAC), we studied tumorigenesis in experimental models of CAC and sporadic CRC that mimic characteristics of human CRC. Using comparative whole genome expression profiling, we observed differential expression of epiregulin (Ereg) in mouse models of colitis-associated, but not sporadic colorectal cancer. Similarly, highly significant upregulation of Ereg expression was found in cohorts of patients with colitis-associated cancer in inflammatory bowel disease but not in sporadic colorectal cancer. Furthermore, tumor-associated fibroblasts were identified as major source of Ereg in colitis-associated neoplasias. Functional studies showed that Ereg-deficient mice, although more prone to colitis, are strongly protected from colitis-associated tumors, and data from serial endoscopic studies revealed that Ereg promotes growth rather than initiation of tumors.
2013-04-01 | GSE43338 | GEO
Project description:Inflammatory caspases are essential effectors of inflammation and cell death. Here, we investigated their roles in colitis and colorectal cancer and report a bimodal regulation of intestinal homeostasis, inflammation and tumorigenesis by caspases-1 and -12. Casp1-/- mice exhibited defects in mucosal tissue repair and succumbed rapidly after dextran sulfate sodium (DSS) administration. This phenotype was rescued by administration of exogenous interleukin-18 and was partially reproduced in mice deficient in the inflammasome adaptor ASC. Casp12-/- mice, in which the inflammasome is derepressed, were resistant to acute colitis and showed signs of enhanced repair. Together with their increased inflammatory response, the enhanced repair response of Casp12-/- mice rendered them more susceptible to colorectal cancer induced by azoxymethane (AOM)+DSS. Taken together, our results indicate that the inflammatory caspases are critical in the induction of inflammation in the gut following injury, which is necessary for tissue repair and maintenance of immune tolerance. Total RNA obtained from isolated tumors or normal colon tissue from wild type and caspase-12 deficient mice were compared.
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Project description:Transcriptome analysis of potential candidate genes and molecular pathways in Et-1-deficient mice with depigmentation
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