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

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

PROVIDER: PRJNA320222 | ENA |

REPOSITORIES: ENA

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

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 using surgical specimens of Japanese FAP patients.

2016-05-03 | GSE80981 | GEO

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

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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

Project description:This SuperSeries is composed of the SubSeries listed below.

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Identification of replicative aging and inflammatory aging signatures via whole-genome CRISPRi screens

Project description:Aging is one of the greatest risk factors for chronic diseases. Research on aging at the cellular level, especially in adult stem cells, is conducive to a comprehensive understanding of the molecular processes of aging. We performed multiple systematic genome-wide CRISPR interference (CRISPRi) screenings in human primary mesenchymal stem cells (MSC) derived from adipose tissues. Notably, we identified potential novel regulators in the progress of MSC senescence in terms of both replicative senescence and inflammatory induced senescence. Combining the functional genomic data with 405 GWAS datasets, including 50 aging-related studies, we observed that the inflammatory aging signatures identified from the CRISPRi screenings were significantly associated with diverse aging processes, suggesting novel signatures to analyze and predict aging status and aging-related disease. These novel signatures verified from the comprehensive functional genomics and genetic datasets may provide targets to interfere with the aging process as well as to improve cell therapy products.

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