Title :

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

Author(s) :

Decourcelle, Amelie [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Very, Ninon [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Djouina, Madjid [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Loison, Ingrid [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Thevenet, Julien [Auteur]
Recherche translationnelle sur le diabète - U 1190 [RTD]
Body-Malapel, Mathilde [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lelièvre, Eric [Auteur]
Senescence Escape and Soluble Markers of Cancer Progression [CRCINA-ÉQUIPE 12]
Coqueret, Olivier [Auteur]
Senescence Escape and Soluble Markers of Cancer Progression [CRCINA-ÉQUIPE 12]
Leprince, Dominique [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Belkoura, Ikram [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Dehennaut, Vanessa [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]

Journal title :

Cancers

Pages :

3168

Publisher :

MDPI

Publication date :

2020

ISSN :

2072-6694

English keyword(s) :

UNC5A
O-GlcNAcylation
OGT
EZH2
nutrition
epigenetics
colon cancer

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hépatologie et Gastroentérologie

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL