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摘要

Nutritional disorders represent major risk factors for colorectal cancer according to mechanisms of action that are still insufficiently known. The aim of our study was to investigate the putative involvement of nutrition in the epigenetic downregulation of the tumor suppressor genes of the UNC5 (Uncoordinated 5) family during colonic carcinogenesis and to understand its molecular relays. Herein, we provided evidence that the consumption of a High Carbohydrate Diet worsens colon carcinogenesis in mice and is correlated with the downregulation of several members of the UNC5 family whose UNC5A (Uncoordinated 5A). Mechanistically, we identified the nutritional sensor O-GlcNAcylation as one of the molecular relays that regulate the recruitment of the PRC2 complex onto the UNC5A promoter to repress its transcription.