Microarray analyses of peripheral whole blood cells from ulcerative colitis patients: Effects of leukocytapheresis

Kobayashi, Teppei; Mitsuyama, Keiichi; Yamasaki, Hiroshi; Masuda, Junko; Takedatsu, Hidetoshi; Kuwaki, Kotaro; Yoshioka, Shinichiro; Nagayama, Koji; Sata, Michio

doi:10.3892/ijmm.2013.1270

Cited by 5 publications

(4 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the sample size of our study is larger, the results are more comprehensive. Some unreported genes still have considerable research value due to their homology with many genes that have been confirmed to be closely related to UC in gene function (Kobayashi et al, 2013; Noble et al, 2008; Planell et al, 2013; Wu et al, 2007). Compared to other data re-analyses researches on UC, almost all of the studies were conducted directly by functional clustering for a large number of DEGs to display the main mechanisms of the disease, which can not reflect the importance of the individual genes (Feng et al, 2017; Song et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Identification of genes and functional coexpression modules closely related to ulcerative colitis by gene datasets analysis

Zhu

Wang

Chen

et al. 2019

PeerJ

View full text Add to dashboard Cite

BackgroundUlcerative colitis is a type of inflammatory bowel disease posing a great threat to the public health worldwide. Previously, gene expression studies of mucosal colonic biopsies have provided some insight into the pathophysiological mechanisms in ulcerative colitis; however, the exact pathogenesis is unclear. The purpose of this study is to identify the most related genes and pathways of UC by bioinformatics, so as to reveal the core of the pathogenesis.MethodsGenome-wide gene expression datasets involving ulcerative colitis patients were collected from gene expression omnibus database. To identify most close genes, an integrated analysis of gene expression signature was performed by employing robust rank aggregation method. We used weighted gene co-expression network analysis to explore the functional modules involved in ulcerative colitis pathogenesis. Besides, biological process and pathways analysis of co-expression modules were figured out by gene ontology enrichment analysis using Metascape.ResultsA total of 328 ulcerative colitis patients and 138 healthy controls were from 14 datasets. The 150 most significant differentially expressed genes are likely to include causative genes of disease, and further studies are needed to demonstrate this. Seven main functional modules were identified, which pathway enrichment analysis indicated were associated with many biological processes. Pathways such as ‘extracellular matrix, immune inflammatory response, cell cycle, material metabolism’ are consistent with the core mechanism of ulcerative colitis. However, ‘defense response to virus’ and ‘herpes simplex infection’ suggest that viral infection is one of the aetiological agents. Besides, ‘Signaling by Receptor Tyrosine Kinases’ and ‘pathway in cancer’ provide new clues for the study of the risk and process of ulcerative colitis cancerization.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of genes and functional coexpression modules closely related to ulcerative colitis by gene datasets analysis

Zhu

Wang

Chen

et al. 2019

PeerJ

View full text Add to dashboard Cite

show abstract

“… 10 , 12 , 15 Previous studies related methylation in the aryl-hydrocarbon receptor repressor ( AHRR ) gene and the Cytochrome P450, family 1, subfamily A1 ( CYP1A1 ) gene to tobacco smoke exposure in both smokers and newborns and most studies, including ours, reported the same CpG as the top signal (cg05575921). 10 , 12 , 15 , 42 , 43 Both AHRR and CYP1A1 are involved in the aryl-hydrocarbon receptor (AhR) pathway, regulating the biological responses to hydrocarbons found in cigarette smoke and xenobiotic metabolism in general. 43 – 45 The myosin-1 G ( MYO1G ) gene is involved in haematopoietic processes and regulation of cell elasticity.…”

Section: Discussionmentioning

confidence: 99%

“… 10 , 12 , 15 , 42 , 43 Both AHRR and CYP1A1 are involved in the aryl-hydrocarbon receptor (AhR) pathway, regulating the biological responses to hydrocarbons found in cigarette smoke and xenobiotic metabolism in general. 43 – 45 The myosin-1 G ( MYO1G ) gene is involved in haematopoietic processes and regulation of cell elasticity. 46 The contactin-associated protein-like 2 ( CNTNAP2 ) gene is involved in the development of the nervous system 47 and in neuropsychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring

Küpers¹,

et al. 2015

View full text Add to dashboard Cite

Background: We examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood.Methods: First, we used cord blood of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip. We performed an epigenome-wide association study for the association between maternal smoking and methylation followed by a mediation analysis of the top signals [false-discovery rate (FDR) < 0.05]. We adjusted both analyses for maternal age, education, pre-pregnancy BMI, offspring’s sex, gestational age and white blood cell composition. Secondly, in 175 exposed and 1248 unexposed newborns from two independent birth cohorts, we replicated and meta-analysed results of eight cytosine-phosphate-guanine (CpG) sites in the GFI1 gene, which showed the most robust mediation. Finally, we performed functional network and enrichment analysis.Results: We found 35 differentially methylated CpGs (FDR < 0.05) in newborns exposed vs unexposed to smoking, of which 23 survived Bonferroni correction (P < 1 × 10-7). These 23 CpGs mapped to eight genes: AHRR, GFI1, MYO1G, CYP1A1, NEUROG1, CNTNAP2, FRMD4A and LRP5. We observed partial confirmation as three of the eight CpGs in GFI1 replicated. These CpGs partly mediated the effect of maternal smoking on birthweight (Sobel P < 0.05) in meta-analysis of GECKO and the two replication cohorts. Differential methylation of these three GFI1 CpGs explained 12–19% of the 202 g lower birthweight in smoking mothers. Functional enrichment analysis pointed towards activation of cell-mediated immunity.Conclusions: Maternal smoking during pregnancy was associated with cord blood methylation differences. We observed a potentially mediating role of methylation in the association between maternal smoking during pregnancy and birthweight of the offspring. Functional network analysis suggested a role in activating the immune system.

show abstract

“…Finally, ADGRE5 interacts with CD55 [60–63], the glycosaminoglycan chondroitin sulfate [64, 65], integrin [66] or CD90 [67] in an isoform-specific manner. Initial functional studies suggest that ADGRE5 is relevant for cell adhesion, migration and invasion [53, 59, 68].…”

Section: Discussionmentioning

confidence: 99%

Identification of ADGRE5 as discriminating MYC target between Burkitt lymphoma and diffuse large B-cell lymphoma

et al. 2019

View full text Add to dashboard Cite

Background MYC is a heterogeneously expressed transcription factor that plays a multifunctional role in many biological processes such as cell proliferation and differentiation. It is also associated with many types of cancer including the malignant lymphomas. There are two types of aggressive B-cell lymphoma, namely Burkitt lymphoma (BL) and a subgroup of diffuse large cell lymphoma (DLBCL), which both carry MYC translocations and overexpress MYC but both differ significantly in their clinical outcome. In DLBCL, MYC translocations are associated with an aggressive behavior and poor outcome, whereas MYC-positive BL show a superior outcome. Methods To shed light on this phenomenon, we investigated the different modes of actions of MYC in aggressive B-cell lymphoma cell lines subdivided into three groups: (i) MYC-positive BL, (ii) DLBCL with MYC translocation (DLBCLpos) and (iii) DLBCL without MYC translocation (DLBCLneg) for control. In order to identify genome-wide MYC-DNA binding sites a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) was performed. In addition, ChIP-Seq for H3K4me3 was used for determination of genomic regions accessible for transcriptional activity. These data were supplemented with gene expression data derived from RNA-Seq. Results Bioinformatics integration of all data sets revealed different MYC-binding patterns and transcriptional profiles in MYC-positive BL and DLBCL cell lines indicating different functional roles of MYC for gene regulation in aggressive B-cell lymphomas. Based on this multi-omics analysis we identified ADGRE5 (alias CD97 ) - a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors - as a MYC target gene, which is specifically expressed in BL but not in DLBCL regardless of MYC translocation. Conclusion Our study describes a diverse genome-wide MYC-DNA binding pattern in BL and DLBCL cell lines with and without MYC translocations. Furthermore, we identified ADREG5 as a MYC target gene able to discriminate between BL and DLBCL irrespectively of the presence of MYC breaks in DLBCL. Since ADGRE5 plays an important role in tumor cell formation, metastasis and invasion, it might also be instrumental to better understand the different pathobiology of BL and DLBCL and help to explain discrepant clinical characteristics of BL and DLBCL. Electronic supplementary material The online version of this article (10.1186/s12885-019-5537-0) contains supplementary material, which is available to authorized users.

show abstract

Microarray analyses of peripheral whole blood cells from ulcerative colitis patients: Effects of leukocytapheresis

Cited by 5 publications

References 55 publications

Identification of genes and functional coexpression modules closely related to ulcerative colitis by gene datasets analysis

Identification of genes and functional coexpression modules closely related to ulcerative colitis by gene datasets analysis

DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring

Identification of ADGRE5 as discriminating MYC target between Burkitt lymphoma and diffuse large B-cell lymphoma

Contact Info

Product

Resources

About