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Identification of aging-associated gene expression signatures that precede intestinal tumorigenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE80984 | GEO | 2016/05/03

SECONDARY ACCESSION(S): PRJNA320222

REPOSITORIES: GEO

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Identification of Aging-Associated Gene Expression Signatures That Precede Intestinal Tumorigenesis.

Project description:Aging-associated alterations of cellular functions have been implicated in various disorders including cancers. Due to difficulties in identifying aging cells in living tissues, most studies have focused on aging-associated changes in whole tissues or certain cell pools. Thus, it remains unclear what kinds of alterations accumulate in each cell during aging. While analyzing several mouse lines expressing fluorescent proteins (FPs), we found that expression of FPs is gradually silenced in the intestinal epithelium during aging in units of single crypt composed of clonal stem cell progeny. The cells with low FP expression retained the wild-type Apc allele and the tissues composed of them did not exhibit any histological abnormality. Notably, the silencing of FPs was also observed in intestinal adenomas and the surrounding normal mucosae of Apc-mutant mice, and mediated by DNA methylation of the upstream promoter. Our genome-wide analysis then showed that the silencing of FPs reflects specific gene expression alterations during aging, and that these alterations occur in not only mouse adenomas but also human sporadic and hereditary (familial adenomatous polyposis) adenomas. Importantly, pharmacological inhibition of DNA methylation, which suppresses adenoma development in Apc-mutant mice, reverted the aging-associated silencing of FPs and gene expression alterations. These results identify aging-associated gene expression signatures that are heterogeneously induced by DNA methylation and precede intestinal tumorigenesis triggered by Apc inactivation, and suggest that pharmacological inhibition of the signature genes could be a novel strategy for the prevention and treatment of intestinal tumors.

| S-EPMC5010213 | biostudies-literature

Identification of aging-associated gene expression signatures that precede intestinal tumorigenesis [mouse]

Project description:Aging-associated gene expression alterations have been implicated in various cancers including colorectal cancer. We examined aging-associated gene expression signatures that precede intestinal tumorigenesis by using the expression level of fluorescent proteins (FPs) as a biomarker of a certain fraction of cells that acquire altered gene expression signatures during aging.

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Identification of aging-associated gene expression signatures that precede intestinal tumorigenesis [human]

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Identification of aging-associated gene expression signatures that precede intestinal tumorigenesis

Project description:Identification of aging-associated gene expression signatures that precede intestinal tumorigenesis

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