Bacteria pathogens drive host colonic epithelial cell promoter hypermethylation of tumor suppressor genes in colorectal cancer.

Microbiome
Xiaoxuan XiaJun Yu

Abstract

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. 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. Our integrative analysis revealed previously unknown epigenetic regulation of TSGs in host cells through inducing DNA ...Continue Reading

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Citations

Dec 22, 2020·IScience·Barath UdayasuryanScott S Verbridge
Feb 25, 2021·Advances in Nutrition·Despoina Eugenia KiousiAlex Galanis
Jan 14, 2021·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Mi Young LimYoung-Do Nam

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Datasets Mentioned

BETA
GSE53051

Methods Mentioned

BETA
biopsy
biopsies
4522
PCR
electrophoresis
ELISA
amplicon sequencing
MBDCap-Seq

Software Mentioned

Trimmomatic
limma R / Bioconductor
sva R /
Bioconductor
BSgenome R /
mem aligner
GENCODE
NbClust R / CRAN
Minfi R /
R pscl

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