Homo sapiens
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PROVIDER: PRJNA369558 | ENA |
REPOSITORIES: ENA
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Project description:KEAP1 overexpressed and NRF2 siRNA knockdown A549 NSCLC cells were used to identify downstream genes of NRF2 pathway separately and by combinatorial analysis. We used triplicate microarrays of transfected A549 cells with mKeap1-GFP for overexpression, siRNAs targeting NRF2 for knockdown and siGFP as control respectively. As a result, we identified several genes which are involved in cancer metabolic functions in these cells. We used microarrays to identify the gene downregulated in both KEAP1 overexpressed and NRF2 siRNA knockdown A549 NSCLC cells and found a subset of downregulated genes which are involved in metabolic functions.
2017-08-02 | GSE94393 | GEO
Project description:Expression data from Keap1 overexpression and Nrf2 knockdown lung cancer cell
| PRJNA277032 | ENA
Project description:The transcription factor NF-E2-related factor 2 (Nrf2) induces cytoprotective genes, but has also been linked to the regulation of hepatic energy metabolism. In order to assess the pharmacological potential of hepatic Nrf2 activation in metabolic disease, Nrf2 was activated over 8 weeks in mice on Western diet using two different siRNAs against kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2. Whole genome expression analysis followed by pathway analysis demonstrated that the suppression of Keap1 expression induced genes that are involved in anti-oxidative stress defense and biotransformation, pathways proving the activation of Nrf2 by the siRNAs against Keap1. The expression of neither fatty acid- nor carbohydrate-handling proteins was regulated by the suppression of Keap1. Metabolic profiling of the animals did also not show effects on plasma and hepatic lipids, energy expenditure or glucose tolerance by the activation of Nrf2. The data indicate that hepatic Nrf2 is not a major regulator of intermediary metabolism in mice. Gene expression profile of mouse liver samples from 8-week-old male C57BL6/J mice (N=24) treated with liver-selective Keap1-specific siRNA (group 1: siKeap1-1, N=8; group 2: siKeap1-2, N=8) or unspecific scrambled control siRNA (group 3: siControl, N=8)
2016-09-01 | E-GEOD-80956 | biostudies-arrayexpress
Project description:The E3 ubiquitin ligase substrate recognition subunit Keap1 mediates the ubiquitination and degradation of the oxidative stress transcription factor NRF2. Approximately 30% of non-small cell lung cancers (NSCLCs) harbor inactivating mutations in Keap1 or activating mutations in NRF2, both of which lead to the stabilization of NRF2 and activation of the downstream antioxidant pathway. Recent studies have found that the oncogenic effects of Keap1 and NRF2 mutations are not entirely equivalent, suggesting that Keap1 may have other regulatory substrates. In previous work, we used affinity immunopurification and mass spectrometry to identify the epigenetic regulator CHD6 as a Keap1-interacting protein, with Keap1 mediating the ubiquitination and degradation of CHD6. NSCLC-derived Keap1 mutants lost the ability to bind and ubiquitinate CHD6. Additionally, CHD6 interacts with NRF2 and promotes the enrichment of NRF2 at the promoters of its target genes, enhancing their transcription.This project aims to elucidate the mechanism by which the abnormal accumulation of CHD6 protein, due to disruption of its Keap1-mediated degradation, drives epigenetic reprogramming in the context of Keap1-mutant NSCLC development and progression. The findings will provide a theoretical basis for the development of NRF2 pathway inhibitors targeting CHD6 as a drug target.
2025-01-01 | GSE284431 | GEO
Project description: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. In summary, this analysis revealed that Nrf2 positively regulates transcription of genes that play key roles in central carbon metabolism. A549 cells were transfected with non targeting NS siRNA or siRNA targeting Nrf2. Mock transfected A549 cells were treated with transfection reagent alone. We had 3 biological replicates for each of the 3 groups. Ninty six hours post transfection, cells were lysed and total RNA was isolated.
2013-07-04 | E-GEOD-38332 | biostudies-arrayexpress
Project description:Nrf2-Keap1 signaling pathway protects cells against photo-oxidative stress. Yet in recent works, its role in melanogenesis together with cell protection functions against oxidative stress has been gaining interest. However, its effect on melanogenesis still has contradictory results from different studies. The aims of our study were to investigate the effect of Keap1 silencing in melanocyte on melanogenesis and its associated mechanism. Primary human epidermal melanocytes and melan-a cell line were used for this experiment. RNA sequencing was done to identify genes involved in melanocyte biology using Keap1 knockdown through siRNA techniques. And melanogenesis and the expression of melanogenesis-associated molecules were evaluated in Keap1 silenced melanocyte to examine the effects of Keap1 on melanogenesis, melanocyte growth, and related pathways. RNA-sequencing data revealed that Keap1 knockdown in primary human epidermal melanocytes (PHEMs) induced cell survival-related gene expression. Additionally, siRNA-mediated inhibition of Keap1 led to upregulation of MITF and melanogenesis-associated molecules along with Nrf2 activation in PHEMs. HO-1, a major gene that is upregulated in RNA-sequencing using Keap1-silenced PHEMs, protected melanocytes against H2O2-induced cell death and upregulated MITF and β-catenin expression. Further, increased expression of melanogenesis-associated molecules after Keap1 silencing was validated to occur through HO-1-associated β-catenin activation in a Keap1 and HO-1 double knockdown experiment. This work suggests that Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated β-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival.
2018-01-20 | GSE93895 | GEO
Project description:To examine the role of NRF2 in accelerating cell proliferation and to identify the target genes responsible for this function, transcriptome analysis was performed using A549 cells, in which NRF2 is constitutively activated. NRF2 was knocked down by siRNA against NRF2, and the gene expression profile was compared with that of A549 cells treated with control siRNA. To exclude off-target effects, three different siRNAs against NRF2 was independently applied. NRF2 siRNA or control siRNA was transfected into A549 cells. Cells were harvested 24 hours after transfection, and total RNA was purified.
2011-04-01 | E-GEOD-28230 | biostudies-arrayexpress
Project description:Comparison of gene expression profiles of A549 cell treated with NRF2 siRNA and control siRNA
| PRJNA139597 | ENA
Project description:To identify Nrf1-dependent and Nrf2-dependent genes in the liver, we examined the gene expression profiles of Nrf1 Alb-CKO, Nrf2 knockout and Keap1 knockdown mouse livers by microarray analyses. Total RNAs from Nrf1dN/-::Alb-Cre, Nrf1dN/+, Nrf2-/-, Nrf2+/+, Keap1KD/- and Keap1KD/+ mouse livers were used for the microarray analyses.
2012-05-17 | E-GEOD-35124 | biostudies-arrayexpress
Project description:Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a potent inhibitor of experimental mammary carcinogenesis and may be an effective, safe chemopreventive agent for use in humans. SFN acts in part on the Keap1/Nrf2 pathway to regulate a battery of cytoprotective genes. In this study transcriptomic and proteomic changes in the estrogen receptor negative, non tumorigenic human breast epithelial MCF10A cell line were analyzed following SFN treatment or KEAP1 knockdown with siRNA using microarray and stable isotopic labeling with amino acids in culture (SILAC), respectively. Changes in selected transcripts and proteins were confirmed by PCR and Western blot in MCF10A and MCF12A cells. There was strong correlation between the transcriptomic and proteomic responses in both the SFN treatment (R=0.679, P<0.05) and KEAP1 knockdown (R=0.853, P<0.05) experiments. Common pathways for SFN treatment and KEAP1 knockdown were xenobiotic metabolism and antioxidants, glutathione metabolism, carbohydrate metabolism and NADH/NADPH regeneration. Moreover, these pathways were most prominent in both the transcriptomic and proteomic analyses. The aldo-keto reductase family members, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, as well as NQO1 and ALDH3A1, were highly upregulated at both the transcriptomic and proteomic level. Collectively, these studies served to identify potential biomarkers that can be used in clinical trials to investigate the initial pharmacodynamic action of SFN in the breast. MCF10A cells were treated with SFN or had KEAP1 knocked down by siRNA.
2011-04-22 | E-GEOD-28813 | biostudies-arrayexpress