P53 suppresses the progression of hepatocellular carcinoma via miR‐15a by decreasing OGT expression and EZH2 stabilization

You, Zhenyu; Peng, Dandan; Cao, Yixin; Zhu, Yuanzhe; Yin, Jianjun; Zhang, Guangxing; Peng, Xiao-Dong

doi:10.1111/jcmm.16792

Cited by 16 publications

(10 citation statements)

References 46 publications

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“…OGT also affected the binding of Ezh2 to promoters of transcription factors in breast cancer cells, but not its stability (Forma et al, 2018). Depending on cell type and tissue, GlcNAcylation of Ezh2 did not affect its association with PRC2 but decreased its enzymatic activity (Lo et al, 2018) or stability (Jiang et al, 2019; Sui et al, 2020; You et al, 2021). Further, OGT-dependent recruitment of PRC2.1 to UNC5 family gene promoters led to their silencing in HCT116 colon cancer cells, which has been linked to the worsening of colorectal cancer by a high carbohydrate diet in mammals (Decourcelle et al, 2020).…”

Section: Discussionmentioning

confidence: 94%

Nutrigenomic Regulation of Sensory Plasticity

Vaziri

Wilinski

Freddolino

et al. 2021

Preprint

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Diet composition has a profound influence on brain physiology and behavior, but the mechanisms through which nutrient information is transmuted into neural changes remain elusive. Here we uncover how the metabolic enzyme O-GlcNAc Transferase (OGT) transforms information about the dietary environment into taste adaptations. We show that in the fly D. melanogaster, OGT decorates the chromatin of the sweet taste neurons and provides the nutrient context to drive changes in chromatin accessibility in response to high dietary sugar. Specifically, we found that OGT cooperates with the epigenetic silencer Polycomb Repressive Complex 2.1 (PRC2.1) to promote nutrient-sensitive variations in chromatin openness; these chromatin dynamics result in changes in gene expression and taste plasticity that are dependent on the catalytic activity of OGT. Parallel nutrigenomic signatures were also observed in the lingual epithelium of rats exposed to high dietary sugar, suggesting that this conserved metabolic-epigenetic pathway may also underlie diet-dependent taste changes in mammals. Together our findings reveal a novel role for nutriepigenetic signaling in the brain: amplifying nutrient perturbations into robust changes in chromatin accessibility and transcriptional output that shape neural and behavioral plasticity.

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Section: Discussionmentioning

confidence: 94%

Nutrigenomic Regulation of Sensory Plasticity

Vaziri

Wilinski

Freddolino

et al. 2021

Preprint

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“…Is OGT directly GlcNAcylating PRC2.1 to modify its repressive drive? Several studies have linked OGT activity with the stability, chromatin occupancy, or catalytic function of Polycomb Group Proteins ( Hart, 2019 ; Olivier-Van Stichelen et al, 2017 ; Chu et al, 2014 ; Sakabe and Hart, 2010 ; Forma et al, 2018 ; Sui et al, 2020 ; Jiang et al, 2019 ; You et al, 2021 ; Decourcelle et al, 2020 ; Gambetta and Müller, 2014 ). Thus, converging evidence suggests that OGT impacts different aspects of PRC2.1 and PcG biology and is broadly consistent with our data.…”

Section: Discussionmentioning

confidence: 99%

Nutrigenomic regulation of sensory plasticity

Sung

Vaziri

Wilinski

et al. 2023

eLife

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Diet profoundly influences brain physiology, but how metabolic information is transmuted into neural activity and behavior changes remains elusive. Here, we show that the metabolic enzyme O-GlcNAc Transferase (OGT) moonlights on the chromatin of the D. melanogaster gustatory neurons to instruct changes in chromatin accessibility and transcription that underlie sensory adaptations to a high-sugar diet. OGT works synergistically with the Mitogen Activated Kinase/Extracellular signal Regulated Kinase (MAPK/ERK) rolled and its effector stripe (also known as EGR2 or Krox20) to integrate activity information. OGT also cooperates with the epigenetic silencer Polycomb Repressive Complex 2.1 (PRC2.1) to decrease chromatin accessibility and repress transcription in the high-sugar diet. This integration of nutritional and activity information changes the taste neurons’ responses to sugar and the flies’ ability to sense sweetness. Our findings reveal how nutrigenomic signaling generates neural activity and behavior in response to dietary changes in the sensory neurons.

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“…196 p53 upregulates microRNA-15a to inhibit OGT-mediated enhancer of zeste homologue 2 stabilisation, which ultimately inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells. 197 UDP-N-acetylglucosamine pyrophosphorylase 1-like 1 directly interacts with OGT in a non-substrate form to affect OGT activity, thereby reducing O-GlcNAcylation of c-Myc to inhibit cell proliferation in hepatoma. 198 Imbalanced O-GlcNAcylation regulates the expression, activation, and activity of transcription factors related to adhesion, invasion and metastasis in hepatocellular carcinoma cells to support cancer metastasis.…”

Section: Hypero-glcnacylation Is Linked To the Pathologic Hallmarks O...mentioning

confidence: 99%

Protein O‐GlcNAcylation: The sweet hub in liver metabolic flexibility from a (patho)physiological perspective

Hu,

Zhang,

et al. 2023

Liver International

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O‐GlcNAcylation is a dynamic, reversible and atypical O‐glycosylation that regulates various cellular physiological processes via conformation, stabilisation, localisation, chaperone interaction or activity of target proteins. The O‐GlcNAcylation cycle is precisely controlled by collaboration between O‐GlcNAc transferase and O‐GlcNAcase. Uridine‐diphosphate‐N‐acetylglucosamine, the sole donor of O‐GlcNAcylation produced by the hexosamine biosynthesis pathway, is controlled by the input of glucose, glutamine, acetyl coenzyme A and uridine triphosphate, making it a sensor of the fluctuation of molecules, making O‐GlcNAcylation a pivotal nutrient sensor for the metabolism of carbohydrates, amino acids, lipids and nucleotides. O‐GlcNAcylation, particularly prevalent in liver, is the core hub for controlling systemic glucose homeostasis due to its nutritional sensitivity and precise spatiotemporal regulation of insulin signal transduction. The pathology of various liver diseases has highlighted hepatic metabolic disorder and dysfunction, and abnormal O‐GlcNAcylation also plays a specific pathological role in these processes. Therefore, this review describes the unique features of O‐GlcNAcylation and its dynamic homeostasis maintenance. Additionally, it explains the underlying nutritional sensitivity of O‐GlcNAcylation and discusses its mechanism of spatiotemporal modulation of insulin signal transduction and liver metabolic homeostasis during the fasting and feeding cycle. This review emphasises the pathophysiological implications of O‐GlcNAcylation in nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and hepatic fibrosis, and focuses on the adverse effects of hyper O‐GlcNAcylation on liver cancer progression and metabolic reprogramming.

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P53 suppresses the progression of hepatocellular carcinoma via miR‐15a by decreasing OGT expression and EZH2 stabilization

Cited by 16 publications

References 46 publications

Nutrigenomic Regulation of Sensory Plasticity

Nutrigenomic Regulation of Sensory Plasticity

Nutrigenomic regulation of sensory plasticity

Protein O‐GlcNAcylation: The sweet hub in liver metabolic flexibility from a (patho)physiological perspective

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