Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development.
Bacterially-Associated Transcriptional Remodelling in a Distinct Genomic Subtype of Colorectal Cancer Provides a Plausible Molecular Basis for Disease Development.
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DOI：
10.1371/journal.pone.0166282
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Blackburn JM
中科院分区：
文献类型：
--
作者：
Lennard KS;Goosen RW;Blackburn JM
特定微生物定植与结直肠癌（CRC）疾病发病机制的相关性日益得到认可，但我们对可能将定植与体内疾病联系起来的潜在分子机制的理解仍然有限。在这里，我们研究了最常研究的CRC相关细菌（产肠球菌性脆弱拟杆菌，pks+大肠杆菌，梭杆菌属，afaC+ E。大肠杆菌、粪肠球菌和肠致病性E.大肠杆菌）和改变的CRC患者的转录组学和甲基化谱，以便深入了解这些细菌在CRC的病因学中的潜在贡献。结果表明，E.粪肠球菌和高水平梭杆菌与CRC的特定转录组亚型相关，其特征在于CpG岛甲基化、微卫星不稳定性和炎症和DNA损伤途径的显著增加。对宿主基因表达中显著的细菌相关变化的分析，无论是在单个基因水平还是途径水平，都揭示了转录重塑，该转录重塑提供了特定细菌定殖与该亚型结直肠癌疾病发展和进展之间的合理机制联系;这些包括在梭杆菌高水平定殖的情况下REG 3A、REG 1A和REG 1 P的上调，以及在大肠杆菌定殖的情况下CXCL 10和BMI 1的上调。粪便对E.这种CRC亚型中的粪杆菌和梭杆菌表明结肠上皮的多种微生物定殖很可能是结肠肿瘤发生的一个重要方面。
The relevance of specific microbial colonisation to colorectal cancer (CRC) disease pathogenesis is increasingly recognised, but our understanding of possible underlying molecular mechanisms that may link colonisation to disease in vivo remains limited. Here, we investigate the relationships between the most commonly studied CRC-associated bacteria (Enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium spp., afaC+ E. coli, Enterococcus faecalis & Enteropathogenic E. coli) and altered transcriptomic and methylation profiles of CRC patients, in order to gain insight into the potential contribution of these bacteria in the aetiopathogenesis of CRC. We show that colonisation by E. faecalis and high levels of Fusobacterium is associated with a specific transcriptomic subtype of CRC that is characterised by CpG island methylation, microsatellite instability and a significant increase in inflammatory and DNA damage pathways. Analysis of the significant, bacterially-associated changes in host gene expression, both at the level of individual genes as well as pathways, revealed a transcriptional remodeling that provides a plausible mechanistic link between specific bacterial colonisation and colorectal cancer disease development and progression in this subtype; these included upregulation of REG3A, REG1A and REG1P in the case of high-level colonization by Fusobacterium, and CXCL10 and BMI1 in the case of colonisation by E. faecalis. The enrichment of both E. faecalis and Fusobacterium in this CRC subtype suggests that polymicrobial colonisation of the colonic epithelium may well be an important aspect of colonic tumourigenesis.
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影响因子：
37.3
作者：
Banerjea A;Ahmed S;Hands RE;Huang F;Han X;Shaw PM;Feakins R;Bustin SA;Dorudi S
通讯作者：
Dorudi S
影响因子：
3
作者：
Barnett MP;McNabb WC;Cookson AL;Zhu S;Davy M;Knoch B;Nones K;Hodgkinson AJ;Roy NC
通讯作者：
Roy NC
影响因子：
7
作者：
Hinoue, Toshinori;Weisenberger, Daniel J.;Laird, Peter W.
通讯作者：
Laird, Peter W.
影响因子：
4.7
作者：
Huycke, MM;Abrams, V;Moore, DR
通讯作者：
Moore, DR
DOI：
10.1111/j.1440-1746.2008.05490.x
发表时间：
2008-08-01
影响因子：
4.1
作者：
Balamurugan, Ramadass;Rajendiran, Ethendhar;Ramakrishna, Balakrishnan S.
通讯作者：
Ramakrishna, Balakrishnan S.