Gene Expression Profile of Colon Mucosa after Cytotoxic Insult in wt and<i> Apc</i>-Mutated Pirc Rats: Possible Relation to Resistance to Apoptosis during Carcinogenesis

Femia, Angelo Pietro; Luceri, Cristina; Lodovici, Maura; Crucitta, Stefania; Caderni, Giovanna

doi:10.1155/2016/1310342

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…The level of interferon is known to play a pivotal role in host protection and immunopathology in response to mucosal pathogens and during inflammation in the gut 36 . In a study in rat colons, cytotoxic insult to the colon mucosa induced increased OAS1 gene expression 37 . According to that study, the OAS gene locus could be related to chronic low-grade inflammation of the colonic wall, which is thought to be the pathophysiology underlying the development of diverticulosis.…”

Section: Discussionmentioning

confidence: 98%

Genome-wide association study of right-sided colonic diverticulosis in a Korean population

Choe

Lee

Chung

et al. 2019

Sci Rep

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Diverticulosis results from complex interactions related to aging, environmental factors and genetic predisposition. Despite epidemiologic evidence of genetic risk factors, there has been no attempt to identify genes that confer susceptibility to colonic diverticulosis. We performed the first genome-wide association study (GWAS) on susceptibility to diverticulosis in a Korean population. A GWAS was carried out in 7,948 healthy individuals: 893 patients and 1,075 controls comprised the test set, and 346 patients and 305 controls comprised the replication set. Diverticulosis was diagnosed by colonoscopy during comprehensive medical check-ups, and single-nucleotide polymorphisms (SNPs) related to diverticulosis were detected with the Affymetrix Axiom KORV1.1-96 Array. In all, 9 SNPs were identified in three SNP aggregates in the test set (P < 10 −3 , within 200 kb) after adjusting for sex. All the SNPs were replicated in the replication set (P < 0.05). Three SNPs were near the WNT4 gene, four near the RHOU gene, and two in the OAS1/3 genes. The top SNP associated with right-sided colonic diverticulosis was rs22538787, located near the WNT4 gene [combined set, P-value = 3.128 × 10 −6 , odds ratio = 1.415 (95% confidence interval: 1.223–1.637)]. These 9 novel SNP alleles associated with the WNT4, RHOU, and OAS1/3 genes are possibly involved in the underlying genetic susceptibility to right-sided diverticulosis. Our results provide basic knowledge about the development of diverticulosis in an Asian population.

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Section: Discussionmentioning

confidence: 98%

Genome-wide association study of right-sided colonic diverticulosis in a Korean population

Choe

Lee

Chung

et al. 2019

Sci Rep

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“…Gene expression data available for the Pirc rat model have been limited to studies looking at expression in the role of cytotoxic insult or the expression profile of canonical cancer-related genes in the normal mucosa (489)(490)(491). We demonstrated here for the first time that congenic Pirc rats show differential gene expression depending on the GM they harbor.…”

Section: Discussionmentioning

confidence: 86%

Unraveling the role of the endogenous complex gut microbiota in the Pirc rat model of human colon cancer

Busi¹

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The gut microbiota (GM) has recently been shown to modulate several systemic conditions in human and model systems, most importantly in intestinal disorders. It has also been demonstrated to have significant impacts on patients' susceptibility to colon cancer. The GM can be defined as the dynamic communities of bacteria, viruses, fungi and archaea that inhabit our gut, skin, and most mucosal surfaces. Considering the fact that the human body is exposed to a large number of microorganisms on a daily basis, the constant flux and dynamic interactions between host genetics and the GM can lead to the variability seen in disease manifestation and susceptibility. This leads to a larger question about the relationship of the GM to model systems, and also whether the constant interactions between the taxa affect the development and progression of disease. Colon cancer is the 3rd leading cause of cancer-related death in the USA. We used embryo rederivation to give isogenic APC-gene mutant Pirc rats, a preclinical model of colon cancer distinct complex GMs to understand its effect on disease susceptibility. In this study, we observed significant differences in intestinal tumor multiplicity based on GM profile. Using 16S rRNA sequencing, we characterized the microbial populations of two distinct GM groups and further determined functional differences by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to identify metabolic differences between GM groups. Colonic epithelium and tumors were simultaneously profiled via RNASeq transcriptome analysis. Metabolomics analysis allowed detection of differential metabolites between GM groups and potential bacterial-modulated biomarkers of tumor susceptibility. Simultaneously, bacterial relative abundances showed taxa correlating with suppression of both tumor growth and phenotype penetrance as early as 1 month of age. To determine the role of individual bacteria Pirc rats were treated with 3 different bacteria associated with reduced or increased adenoma burden namely, Desulfovibrio vulgaris Hildenborough, Prevotella copri, and Fusobacterium nucleatum. The work outlined here addresses adenoma development in Pirc rats to identify the potential relationship between these taxa and the endogenous, complex GM through multiple approaches. The research presented in this dissertation may potentially help unravel the molecular mechanisms contributing to disease susceptibility, and could identify therapeutic targets and biomarkers for early non-invasive detection and treatment of colon cancer.

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Early molecular events associated with liver and colon sub-acute responses to 1,2-dimethylhydrazine: Potential implications on preneoplastic and neoplastic lesion development

et al. 2020

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Gene Expression Profile of Colon Mucosa after Cytotoxic Insult in wt and Apc-Mutated Pirc Rats: Possible Relation to Resistance to Apoptosis during Carcinogenesis

Cited by 3 publications

References 27 publications

Genome-wide association study of right-sided colonic diverticulosis in a Korean population

Genome-wide association study of right-sided colonic diverticulosis in a Korean population

Unraveling the role of the endogenous complex gut microbiota in the Pirc rat model of human colon cancer

Early molecular events associated with liver and colon sub-acute responses to 1,2-dimethylhydrazine: Potential implications on preneoplastic and neoplastic lesion development

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