从基因组到表观基因组,菌群如何影响结肠癌(综述)
  • 菌群产生的毒素可直接导致DNA损伤,引起染色质不稳定,激活原癌基因;
  • 菌群直接或间接引起DNA异常甲基化,引发与结肠癌(CRC)相关的通路失调;
  • 菌群通过修饰组蛋白来改变转录因子结合位点的可及性,引起CRC有关基因的启动子和增强子区域发生变化;
  • 菌群还可改变致癌或抑癌miRNA以及lncRNA的表达,从而影响G偶联蛋白受体和转化生长因子信号通路;
  • 深化了解菌群影响CRC的机制有助于预防、早期检测或靶向治疗CRC。
主编推荐语
小肠君
肠道菌群与结直肠癌发生发展显著相关。《Genome Medicine》近期发表研究,回顾了肠道菌群影响宿主结直肠癌相关基因、表观遗传、基因表达等的研究,系统性总结了相关作用机制,对于开发预防、检测或靶向治疗结直肠癌的新方法具有参考价值。
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Genome Medicine [IF:15.266]

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

菌群对肠上皮细胞基因组和表观基因组的影响:对结直肠癌发展的贡献

10.1186/s13073-019-0621-2

2019-02-25, Review

Abstract & Authors:展开

Abstract:收起
In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer-related deaths globally. Hence, a more in-depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care.

First Authors:
Jawara Allen

Correspondence Authors:
Cynthia L Sears

All Authors:
Jawara Allen,Cynthia L Sears

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