In conclusion, we provided evidences that the nutritional sensor O-GlcNAcylation represents one of the molecular relays between nutritional disorders and the epigenetic downregulation of key tumor suppressor genes driving the progression of colorectal carcinogenesis including UNC5A. In the near future, it will therefore be interesting to investigate whether strategies targeting O-GlcNAcylation could represent a new therapeutic hope in the treatment of colorectal cancer. Here, UNC5A is linked to nutritional disorder.