Transcriptional Analysis of Left-sided Colitis, Pancolitis, and Ulcerative Colitis-associated Dysplasia

Bjerrum, Jacob Tveiten; Nielsen, Ole Haagen; Riis, Lene; Pittet, Valérie; Mueller, Christoph; Rogler, Gerhard; Olsen, Jørgen

doi:10.1097/mib.0000000000000235

Cited by 31 publications

(36 citation statements)

References 42 publications

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“…In fact, we have previously revealed that the expression of CDX2 becomes significantly down‐regulated during inflammation in patients with UC [Coskun et al, ]. Additionally, other studies have reported an increased expression of LAMC2 in patients with UC [Toedter et al, ; Bjerrum et al, ]. In agreement with these findings, exposure of Caco‐2 cells to TNF‐α down‐regulates the expression of CDX2 and enhances the expression of LAMC2 [Coskun et al, ; Boyd et al, ].…”

Section: Discussionsupporting

confidence: 67%

“…Altered expression profiles of several laminin subunits have been reported in patients with IBD and experimental colitis [Bouatrouss et al, ; Schmehl et al, ; Koutroubakis et al, ; Toedter et al, ; Bjerrum et al, ; Spenle et al, ]. Moreover, genomic loci linked to the LAMB1 gene has specifically been found to strongly associate with UC‐susceptibility [Thompson et al, ].…”

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confidence: 99%

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Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

et al. 2016

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The expression of Caudal-related homeobox transcription factor 2 (CDX2) is impaired by tumor necrosis factor-α (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) in ulcerative colitis (UC). Laminin subunit γ2 (LAMC2) is an epithelial basement membrane protein implicated in cell migration, proliferation, differentiation, as well as tumor invasion and intestinal inflammation, and its expression is enhanced by TNF-α in a NF-κB-dependent regulation of the recently identified LAMC2 enhancer. The aim was to determine whether CDX2 is involved in the basal regulation of LAMC2 in epithelial cells and to assess the influence of inflammation. Transcriptional regulation of LAMC2 was examined by reporter gene assays, overexpression, and shRNA-mediated knock-down of CDX2. CDX2-DNA interactions were assessed by chromatin immunoprecipitation on Caco-2 cells without or with TNF-α, as well as in purified colonic human epithelial cells. Immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction analyses were used to measure the expression of CDX2 and LAMC2 in colonic biopsies from healthy controls and patients with UC. These data indicate that CDX2 directly regulates LAMC2 gene expression through interaction with elements in the LAMC2 promoter region. We further revealed an inverse effect of inflammation on CDX2 and LAMC2. The data presented provide a novel insight into how CDX2 is implicated in the transcriptional regulation of LAMC2 in intestinal epithelial cells, a function that is impaired during mucosal inflammation where a high level of TNF-α is present. J. Cell. Biochem. 118: 298-307, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 67%

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confidence: 99%

Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

et al. 2016

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“…Based on a PCA model containing the first three PCs of this initial PCA, a Hotelling T 2 test was performed comparing CI_WT with CI_KO and UT_WT with UT_KO, respectively. The Hotelling T 2 test was performed using a multiple linear regression model in R, as previously described 23 . A second PCA was subsequently performed including only the inflamed samples.…”

Section: Methodsmentioning

confidence: 99%

Cytoglobin affects tumorigenesis and the expression of ulcerative colitis-associated genes under chemically induced colitis in mice

Yassin

Kissow

Vainer

et al. 2018

Sci Rep

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Cytoglobin (Cygb) is a member of the hemoglobin family and is thought to protect against cellular hypoxia and oxidative stress. These functions may be particularly important in inflammation-induced cancer, e.g., in patients with ulcerative colitis (UC). In this study, we investigated the development of inflammation and tumors in a murine model of inflammation-induced colorectal cancer using a combined treatment of azoxymethane and dextran sulfate sodium. A bioinformatics analysis of genome-wide expression data revealed increased colonic inflammation at the molecular level accompanied by enhanced macroscopic tumor development in Cygb-deficient mice. Moreover, the expression of the UC-associated gene neurexophilin and PC-esterase domain family member 4 (Nxpe4) depended on the presence of Cygb in the inflamed colonic mucosa. Compared to wild type mice, RT-qPCR confirmed a 14-fold (p = 0.0003) decrease in Nxpe4 expression in the inflamed colonic mucosa from Cygb-deficient mice. An analysis of Cygb protein expression suggested that Cygb is expressed in fibroblast-like cells surrounding the colonic crypts. Histological examinations of early induced lesions suggested that the effect of Cygb is primarily at the level of tumor promotion. In conclusion, in this model, Cygb primarily seemed to inhibit the development of established microadenomas.

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“…A total of 12 microarray data sets were downloaded from the Gene Expression Omnibus database ( ), which included GSE3365 ( 10 ), GSE36807 ( 11 ), GSE37283 ( 12 ), GSE38713 ( 13 ), GSE42911, GSE47908 ( 14 ), GSE48634 ( 15 ), GSE48959 ( 16 ), GSE59071 ( 17 ), GSE6731 ( 18 ), GSE71730 ( 19 ), and GSE9452 ( 20 ) ( Table I ). The microarray data sets were selected according to following criteria: i) Expression profiling by array contain that compare samples from patients with UC and normal group; ii) samples in the UC group were obtained from patients whom did not receive any interventions or treatments; and iii) DEGs were statistically significantly different between the UC group and the normal control group, with a threshold of P<0.05 indicating a statistically significant difference and |log 2 (FC)|>1, where FC is fold change.…”

Section: Methodsmentioning

confidence: 99%

Integrated strategy of differentially expressed genes associated with ulcerative colitis

Feng

Gao

Liu

et al. 2017

Molecular Medicine Reports

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with both genetic and environmental factors; however, the underlying pathogenesis of UC remains unclear. The present study aimed to further explore 12 microarray datasets from patients with UC obtained from the Gene Expression Omnibus repository, for potential genetic pathogenesis of UC through a global bioinformatics view, which included identification of differentially expressed genes (DEGs), functional enrichments, protein-protein interactions, transcriptional and post-transcriptional regulation and drug-gene associations. This integrated analysis screened 233 DEGs that were compared between UC and normal control tissue samples; these included 173 upregulated and 60 downregulated DEGs. Subsequently, transcription factors, such as TATA-binding protein 1 (TBP1; hsa_TATAAA_V$TATA_01) and nuclear factor-κB (NF-κB; hsa_V$NFKAPPAB_01) and microRNAs (miRNAs; such as miR-516-3p and miR-23a) were revealed to be associated with 233 DEGs. Notably, further analysis indicated that these DEGs were enriched in certain diseases, including inflammation, fibrosis and immune system diseases, and were also associated with some drugs, including prednisone, collagenase and mycophenolate mofetil, which may provide choice for treatment of UC. In conclusion, this study may provide novel insights into discovering potential molecular targets involved in the pathogenesis and treatment of UC.

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Transcriptional Analysis of Left-sided Colitis, Pancolitis, and Ulcerative Colitis-associated Dysplasia

Cited by 31 publications

References 42 publications

Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

Cytoglobin affects tumorigenesis and the expression of ulcerative colitis-associated genes under chemically induced colitis in mice

Integrated strategy of differentially expressed genes associated with ulcerative colitis

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