Transcriptomics

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Deletion of TNF in Winnie-ApcMin/+ mice reveals its protective role in the progression of colorectal cancer


ABSTRACT: To examine the effects of chronic, low-grade inflammation on the pathogenesis of colorectal cancer (CRC), we developed a novel murine model of colitis-associated cancer by crossing Winnie mice with ApcMin/+ mice thus combining the inflammatory background with a genetic predisposition to develop small intestinal polyposis, respectively. Winnie-ApcMin/+ mice showed early, spontaneous occurrence of colonic dysplastic lesions with a distinct molecular signature. Since TNF is a major clinical target for suppression of chronic intestinal inflammation, we investigated its impact on Winnie-ApcMin/+ model. Surprisingly, deletion of Tnf in Winnie-ApcMin/+ mice resulted in an initial reduction of dysplastic lesions at disease onset, but facilitated disease progression with a unique molecular footprint. Our results confirm that even a mild, but chronic, inflammation represents a crucial risk factor in individuals genetically-predisposed to CRC, and support a dual role for TNF in the onset vs. progression towards CRC.

ORGANISM(S): Mus musculus

PROVIDER: GSE138722 | GEO | 2021/12/31

REPOSITORIES: GEO

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