GEO DataSets

(Submitter supplied) To understand how hyperactive NRF2 causes the esophageal phenotype in mice.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

4 Samples

Download data: TXT

(Submitter supplied) We analyzed the esophagus of Keap1 conditional knockout mice. In these mice, there were both Keap1-normal and Keap1-deleted cells in the esophageal epithelium. To compare the gene expression of these cells, we conducted single-cell RNA-seq for the mice esophagus.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL28457

2 Samples

Download data: CSV

(Submitter supplied) Clinical evidence has revealed that high-level activation of NRF2 caused by somatic mutations in NRF2 is frequently detected in esophageal squamous cell carcinoma (ESCC), whereas that by somatic mutations in KEAP1, a negative regulator of NRF2, is not. Here, we challenged to generate a mouse model of NRF2-activated ESCC using the cancer-derived NRF2L30F mutation and cancer-driver mutant Trp53R172H. Concomitant expression of NRF2L30F and Trp53R172H induced proliferation of squamous cell epithelia and resulted in NRF2-activated ESCC-like lesions. In contrast, while squamous cell-specific deletion of KEAP1 induced similar NRF2 hyper-activation, the loss-of-KEAP1 combined with Trp53R172H did not elicit the proliferation and formation of ESCC-like lesions. Instead, KEAP1-deleted cells disappeared from the esophageal epithelium over time by cell competition. These findings provide insights into the observation that somatic mutations are more frequently observed in NRF2 than in KEAP1, and the mouse model developed here will be instrumental in elucidating the mechanistic basis leading to NRF2-activated ESCC.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL28457

25 Samples

Download data: TXT

(Submitter supplied) Transcriptional profiling of mouse esophageal development. Goal was to globally profile critical genes and signaling pathways during the development of mouse esophagus and determine how Nrf2/Keap1 pathway regulates the morphogenesis of the esophageal epithelium.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL7202

27 Samples

Download data: TXT

(Submitter supplied) Activation of Wnt/β-catenin signaling is frequent in human and rodent hepatocarcinogenesis. Although in mice, the tumor promoting activity of agonists of constitutive androstane receptor (CAR) occurs via selection of carcinogen-initiated cells harbouring β-catenin mutations, the molecular alterations leading to hepatocellular carcinoma (HCC) development by The CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), in the absence of genotoxic injury are unknown. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6887

22 Samples

Download data: TXT

(Submitter supplied) The Keap1/Nrf2 signaling pathway is a tractable target for the pharmacological prevention of tumorigenesis. 3H-1,2-dithiole-3-thione (D3T) and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) are representative members of two classes of Nrf2-activating chemopreventive agents. Natural dithiolethiones have been widely used in clinical trials for cancer chemoprevention. Synthetic triterpenoids, however, have been shown to be significantly more potent Nrf2 activators and are under clinical evaluation for the treatment of chronic kidney disease. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

40 Samples

Download data: CEL

(Submitter supplied) Glycolysis is a master regulator of cellular energy, synthesis and redox regulation, however the mechanisms that underlie the responses to and regulation of changing glucose metabolism are incompletely understood. The NRF2-antioxidant response element (ARE) pathway serves as a central regulator of cellular stress by sensing and eliminating 2 chemically reactive species in the cell. A phenotypic high-throughput chemical screen for novel activators of NRF2 signaling identified an inhibitor of the glycolytic enzyme PGK1. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: XLSX

(Submitter supplied) To study the effects of NRF2 inhibitors (pyrimethamine or mitoxantrone) on human esophageal squamous cell carcinoma cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

12 Samples

Download data: CSV

(Submitter supplied) To study the effects of NRF2 inhibitors (pyrimethamine) on mRNA expression in mouse esophageal epithelium.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

11 Samples

Download data: TXT

(Submitter supplied) We found that Keap1-Nrf2 signaling pathway mediates UBR7 to regulate HK2 expression through the modification of histone H2BK120 monoubiquitination, thereby inhibiting glycolysis and HCC tumorigenesis.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

6 Samples

Download data: TXT

(Submitter supplied) We found that Keap1-Nrf2 signaling pathway mediates UBR7 to regulate HK2 expression through the modification of histone H2BK120 monoubiquitination, thereby inhibiting glycolysis and HCC tumorigenesis.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24247

2 Samples

Download data: TXT

(Submitter supplied) Transcriptional profiling of adult esophageal epithelium comparing wild-type mice with Nrf2-/- mice with or without gastroesophageal reflux for 4 weeks. Goal was to determine the role of Nrf2 on the barrier function of mouse esophageal epithelium.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL7202

24 Samples

Download data: TXT

(Submitter supplied) Arsenic (iAs) induces generation of the cancer stem-like cells (CSCs) through Nrf2-dependent HIF1α activation, and the subsequent metabolic reprogramming from mitochondrial oxdaive phosphorylation to glycolysis in epithelial cells.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

5 Samples

Download data: BED

(Submitter supplied) Considerable advances have been made in lung cancer therapies, but there is still an unmet clinical need to improve survival for lung cancer patients. Immunotherapies have improved survival, although only 20-30% of patients respond to these treatments. Interestingly, cancers with mutations in KEAP1, the negative regulator of the NRF2 cytoprotective pathway, are resistant to immune checkpoint inhibition and correlate with decreased immune cell infiltration. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

15 Samples

Download data: TXT

(Submitter supplied) To elucidate the mechanisms by which Nrf2 regulates cell growth, we performed global gene expression profiling of A549 lung cancer cells with knockdown of Nrf2. Gene networks associated with carbohydrate metabolism and drug metabolism were significantly downregulated in Nrf2-depleted A549 cells. Gene Set Enrichment Analysis revealed significant enrichment of genes associated with carbohydrate catabolic processes, positive regulation of metabolic processes, PPP, and arachidonic acid metabolism. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

9 Samples

Download data: CEL

(Submitter supplied) Oltipraz is an activator of Nrf2 but is also an activator of other pathways including those mediated by constitutive activated receptor (CAR). To identify genes regulated by oltipraz that were Nrf2-dependent, we compared gene expression after exposure in wild-type and Nrf2-null mice.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6096

16 Samples

Download data: CEL, TXT

(Submitter supplied) The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9185

3 Samples

Download data: TXT, WIG

(Submitter supplied) The NRF2 pathway is frequently activated in various cancer types, yet a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a robust NRF2 activity metric and utilized it to conduct a pan-cancer wide analysis of oncogenic NRF2 signaling. We identified a distinct immunoevasive phenotype where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression and T-cell infiltration spanning non-small cell lung cancer (NSCLC) and squamous malignancies of head and neck area, cervix and esophagus. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

9 Samples

Download data: TXT

(Submitter supplied) We report whole transcriptomic differences between B cells from PPBL patients and marginal zone like B cells from healthy donors using next generation RNA-sequencing

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

7 Samples

Download data: XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL11154 GPL24676

16 Samples

Download data: TXT