EBV infection alters DNA methylation in primary human colon cells: a path to inflammation and carcinogenesis?
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PROVIDER: PRJNA1136848 | ENA |
REPOSITORIES: ENA
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Project description:EBV is associated to several types of human cancers and changes in DNA methylation are reported to contribute to viral-driven carcinogenesis, particularly in cancers of epithelial origin. In previous study, we have shown that EBV infects human primary colonic cells (HCoEpC) and replicates in these cells, inducing pro-inflammatory and pro-tumorigenic effects, mostly prevented by inhibiting viral replication by PAA. Interestingly, the EBV-induced effects correlated with DNMT1 upregulation and were counteracted by pretreating cells by 5-AZA, suggesting a role for DNA hypermethylation. Based on this background, in this study, we investigated the methylation changes induced by EBV infection in HCoEpC, in the presence or in the absence of PAA or ERK1/2 and STAT3 inhibitors, pathways known to be activated by EBV and involved in dysregulating methylation in tumor cells. The genome wide-methylation analysis performed in this study allowed us to identify several biological processes and genes affected by this epigenetic change, as a possible underlying mechanism leading to the pathologic effects induced by EBV previously observed. In particular, we found that the virus induced intense methylation changes, that hypermethylation was prevalent over hypomethylation, and that several genes involved in embryogenesis and carcinogenesis and inflammation were affected.
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Project description:MicroRNA (miRNA) expression profiles for colon cancers were examined to investigate the miRNA involvement in colon carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate colon cancers from noncancerous colon tissues.
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Project description:The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers.
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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
Project description:The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers. There were two major objectives for this study. The first objective was to determine whether EBV infected cells exhibiting type I latency influence cellular microRNA expression. For this study, four EBV negative derivatives of the type I latency cell line, Mutu I, were derived by retroviral infection with a dominant negative from of the EBV episomal replication factor, EBNA1. RNA from these four clones were compared to parental EBV positive Mutu I cells. Four dual labeling experiments were carried out for this comparison with dye reversal for every second pair of RNAs. The second objective was to determine whether EBV type III latency cells exhibit altered cellular microRNA gene expression compared to type I latency cells or EBV negative B cells. Four dual labeling experiments were carried out for this analysis with dye reversal for every second pair of RNAs.
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2017-11-01 | GSE102389 | GEO
Project description:We proposed that the frequency of EBV reactivation may be crucial for its pathogenic role and highly recurrent EBV reactivations exert a profound influence on genome instability. Recurrent reactivations were induced in the EBV-latently infected NPC cells (NA cells) by treating with 12-o-tetradecanoylphorbol-13-acetate (TPA) and sodium n-butyrate (SB) once per passage periodically. Genome-wild oligoarray-based comparative genomic hybridization (CGH) technology was applied to investigate the copy-number aberrations in response for different frequencies of EBV reactivation. The results showed that the NR15 cells, NA cells with the highest frequency (15 times) of reactivation, exhibit extensive genomic copy-number alterations (CNAs) mostly involving chromosome 3p, 3q, 8p, 8q, 9p and 9q, whereas limited number of CNAs were observed both in NR1 cells where only the initial reactivation take place and NP15 cells which were culture in parallel with NR15 cells without EBV-reactivation. We concluded that it is the highly recurrent reactivations of EBV, but neither just a primary reactivation nor EBV-latent infection, may intimately involve in carcinogenesis of nasopharyngeal epithelial cells with the progressive genome instabilities and the accumulation of genetic mutations. Keywords: array-based comparative genomic hybridization, reactivation of EBV, incidence, frequency, recurrent, genome instability, copy-number alterations, carcinogenesis, and nasopharyngeal carcinoma (NPC).
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Project description:Microbiome sequencing of the Atlantic PATH cohort
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Project description:In this study, we analyzed global gene expressions of colon tumors from DNA hypomethylated and the control mice. We found that DNA hypomethylated tumors express significantly higher levels of intestinal differentiation-related genes when compared with the control tumors. These results suggest that DNA methylation may play a role in the maintenance of undifferentiated state of colon tumor cells. Two different Dnmt1 mutant alleles were used in this study; hypomorphic Dnmt1chip allele and conventional KO Dnmt1c allele, which described previously. Previous studies indicated that Dnmt1chip/c mice have reduced DNA methylation contents at pericentromeric satellite repeats, while Dnmt1chip/+ mice have the same levels of genomic methylation as wildtype mice. Experimental mice in an isogenic F1 hybrid background were obtained by breeding Dnmt1c/+; ApcMin/+ mouse in the C57BL/6 background with Dnmt1chip/chip; Apc+/+ mouse in the 129Sv4 background. Six-week-old DNA hypomethylated (Dnmt1chip/c; ApcMin/+) and the control (Dnmt1chip/+; ApcMin/+) mice were fed with 2% (w/v) dextran sodium sulfate (DSS), a potent promoter for colon carcinogenesis. At 20 weeks of age, colon tumors were harvested from both cohorts (n=3 for both DNA hypomethylated tumors and the control tumors) and analyzed for their gene expressions.
2015-08-05 | E-GEOD-60620 | biostudies-arrayexpress