期刊
MICROBIOME
卷 8, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s40168-020-00847-4
关键词
Colorectal cancer; Microbiota; DNA methylation; MBDCap-Seq; DNMT
类别
资金
- Science and Technology Program Grant Shenzhen [JCYJ20170413161534162]
- HMRF Hong Kong [17160862]
- RGC-CRF Hong Kong [C4039-19G]
- RGC-GRF Hong Kong [14163817]
- Vice-Chancellor's Discretionary Fund CUHK
- CUHK direct grant
- Shenzhen Virtual University Park Support Scheme
- National Natural Science Foundation of China [31871340]
Background: Altered microbiome composition and aberrant promoter hypermethylation of tumor suppressor genes (TSGs) are two important hallmarks of colorectal cancer (CRC). Here we performed concurrent 16S rRNA gene sequencing and methyl-CpG binding domain-based capture sequencing in 33 tissue biopsies (5 normal colonic mucosa tissues, 4 pairs of adenoma and adenoma-adjacent tissues, and 10 pairs of CRC and CRC-adjacent tissues) to identify significant associations between TSG promoter hypermethylation and CRC-associated bacteria, followed by functional validation of the methylation-associated bacteria. Results: Fusobacterium nucleatum and Hungatella hathewayi were identified as the top two methylation-regulating bacteria. Targeted analysis on bona fide TSGs revealed that H. hathewayi and Streptococcus spp. significantly correlated with CDX2 and MLH1 promoter hypermethylation, respectively. Mechanistic validation with cell-line and animal models revealed that F. nucleatum and H. hathewayi upregulated DNA methyltransferase. H. hathewayi inoculation also promoted colonic epithelial cell proliferation in germ-free and conventional mice. Conclusion: Our integrative analysis revealed previously unknown epigenetic regulation of TSGs in host cells through inducing DNA methyltransferase by F. nucleatum and H. hathewayi, and established the latter as CRC-promoting bacteria.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据