O-GlcNAcylation Links Nutrition to the Epigenetic Downregulation of UNC5A during Colon Carcinogenesis - Centre de Recherche en Cancérologie et Immunologie Nantes Angers Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2020

O-GlcNAcylation Links Nutrition to the Epigenetic Downregulation of UNC5A during Colon Carcinogenesis

Résumé

While it is now accepted that nutrition can influence the epigenetic modifications occurring in colorectal cancer (CRC), the underlying mechanisms are not fully understood. Among the tumor suppressor genes frequently epigenetically downregulated in CRC, the four related genes of the UNC5 family: UNC5A, UNC5B, UNC5C and UNC5D encode dependence receptors that regulate the apoptosis/survival balance. Herein, in a mouse model of CRC, we found that the expression of UNC5A, UNC5B and UNC5C was diminished in tumors but only in mice subjected to a High Carbohydrate Diet (HCD) thus linking nutrition to their repression in CRC. O-GlcNAcylation is a nutritional sensor which has enhanced levels in CRC and regulates many cellular processes amongst epigenetics. We then investigated the putative involvement of O-GlcNAcylation in the epigenetic downregulation of the UNC5 family members. By a combination of pharmacological inhibition and RNA interference approaches coupled to RT-qPCR (Reverse Transcription-quantitative Polymerase Chain Reaction) analyses, promoter luciferase assay and CUT&RUN (Cleavage Under Target & Release Using Nuclease) experiments, we demonstrated that the O-GlcNAcylated form of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) represses the transcription of UNC5A in human colon cancer cells. Collectively, our data support the hypothesis that O-GlcNAcylation could represent one link between nutrition and epigenetic downregulation of key tumor suppressor genes governing colon carcinogenesis including UNC5A.
Fichier principal
Vignette du fichier
P20.26 Article 2020_cancers.pdf (2.81 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03110218 , version 1 (14-01-2021)

Licence

Paternité

Identifiants

Citer

Amelie Decourcelle, Ninon Very, Madjid Djouina, Ingrid Loison, Julien Thevenet, et al.. O-GlcNAcylation Links Nutrition to the Epigenetic Downregulation of UNC5A during Colon Carcinogenesis. Cancers, 2020, Cancers, 12 (11), pp.3168. ⟨10.3390/cancers12113168⟩. ⟨hal-03110218⟩
167 Consultations
100 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More