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NRF2 Integrates Metabolic, Epigenetic and Oncogenic Regulation in Driving Liver Cancer Progression

ABSTRACT: NRF2 Integrates Metabolic, Epigenetic and Oncogenic Regulation in Driving Liver Cancer Progression

PROVIDER: PRJNA761720 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15817081_1.fastq.gz	Fastqsanger.gz
	SRR15817081_2.fastq.gz	Fastqsanger.gz
	SRR15817082_1.fastq.gz	Fastqsanger.gz
	SRR15817082_2.fastq.gz	Fastqsanger.gz
	SRR15817083_1.fastq.gz	Fastqsanger.gz

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NRF2 Integrates Metabolic, Epigenetic and Oncogenic Regulation in Driving Liver Cancer Progression

Project description:The expression of NRF2 was activated in human hepatocellular carcinoma. In current study, we observed that in hepatic carcinogen diethylnitrosamine induced liver tumor mouse model, NRF2 knockout mouse developed less liver tumor incidence than wild type mouse. To reveal the detailed mechanism, RNA-seq experiment was conducted to compare gene transcriptome profiles of NRF2 WT and KO mice during HCC progression.

2021-09-15 | GSE183712 | GEO

Nrf2 drives hepatocellular carcinoma progression through acetyl-CoA-mediated metabolic, epigenetic and oncogenic regulatory networks

Project description:Liver tumors had high levels of histone acetylation. Nrf2 knockout mice developed fewer tumors than Nrf2 wild-type mice. The mechanistic study found that Nrf2 knockout reduced the generation of acetyl CoA from impaired glycolysis, TCA cycle, and fatty acid metabolism. Acetyl CoA is the substrate for protein acetylation including histone acetylation. Here we determined the genome-wide distribution of AcH3K27. We found that Nrf2 through regulating acetyl CoA production affects histone acetylation (AcH3K27) to modulate the expression of genes, whose products were involved in the glycolysis, TCA cycle, fatty acid metabolism, and oncogenic Myc/mTor signaling. Our findings supported an Nrf2-integrated metabolic, epigenetic and oncogenic signaling in driving liver tumor development.

2023-03-20 | GSE227068 | GEO

NRF2 integrates metabolic and epigenetic regulation in liver cancer

Project description:NRF2 integrates metabolic and epigenetic regulation in liver cancer

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NRF2 is a spatiotemporal metabolic hub driving the polyfunctionality of Th2 cells in allergic asthma

Project description:Polyfunctional T cell responses are detrimental in immune disorders; however, it is unclear how effector T cell subsets acquire polyfunctionality in tissues. Here, we demonstrate that the activation of Nrf2 is necessary for the differentiation polyfunctional Th2 cells in vivo. Reactive oxygen species (ROS) levels are significantly elevated in lung-infiltrating immune cells during allergic asthma, and inhibiting either ROS or Nrf2 significantly decreases eosinophilia and polyfunctional Th2 cells in the lung. In vivo studies using multiple cell-type specific Nrf2-deficient mice and mixed bone marrow chimeras revealed that cell-intrinsic Nrf2 drives IL-5 and IL-13 expression in Th2 cells independently of IL-33. Mechanistically, Nrf2 promotes optimal OXPHOS and glycolysis capacity by inducing PPARg expression and glucose uptake to drive polyfunctionality of Th2 cells. Blocking Nrf2 reduces IL-5 and IL-13 production from house dust mite allergen-specific Th2 cells obtained from asthma patients. These findings demonstrate that Nrf2 acts as a spatiotemporal metabolic hub driving the differentiation of polyfunctional Th2 cells, which may have therapeutic implications for controlling allergic lung inflammation.

2023-08-24 | GSE241138 | GEO

NRF2 is a spatiotemporal metabolic hub driving the polyfunctionality of Th2 cells in allergic asthma

Project description:Polyfunctional Th2 cells play a crucial role in triggering diverse pathogenic responses in allergic diseases by producing multiple cytokines. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of Nrf2 in polyfunctional Th2 cells during allergic asthma. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma. Deletion of the ROS sensor Nrf2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, Nrf2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality, partially by inducing PPARγ, independently of IL-33. Treatment with an Nrf2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice, and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells (PBMCs) in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.

2023-08-25 | GSE241355 | GEO

The oncogenic action of NRF2 depends on de-glycation by Fructosamine-3-kinase (FN3K)

Project description:We show that NRF2 activation drives hepatocellular carcinoma development in vivo. Moreover, NRF2 undergoes glucose dependent modification called glycation and requires the de-glycating enzyme FN3K to maintain NRF2' oncogenic functions.

2019-06-22 | GSE133160 | GEO

Nrf2 drives hepatocellular carcinoma progression through acetyl-CoA-mediated metabolic, epigenetic and oncogenic regulatory networks

Project description:Nrf2 drives hepatocellular carcinoma progression through acetyl-CoA-mediated metabolic, epigenetic and oncogenic regulatory networks

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NRF2 is a spatiotemporal metabolic hub driving the polyfunctionality of Th2 cells in allergic asthma

Project description:NRF2 is a spatiotemporal metabolic hub driving the polyfunctionality of Th2 cells in allergic asthma

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NRF2 is a spatiotemporal metabolic hub driving the polyfunctionality of Th2 cells in allergic asthma

Project description:NRF2 is a spatiotemporal metabolic hub driving the polyfunctionality of Th2 cells in allergic asthma

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Nrf2 transcript alterations

Project description:WGS and RNA-seq data for Nrf2 study

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