m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00348)
Target Name Nuclear factor erythroid 2-related factor 2 (NFE2L2)
Synonyms
NF-E2-related factor 2; NFE2-related factor 2; Nrf-2; HEBP1; Nuclear factor, erythroid derived 2, like 2; NRF2
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Gene Name NFE2L2
Chromosomal Location 2q31.2
Family bZIP family; CNC subfamily
Function
Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes. The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes. May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region. Plays also an important role in the regulation of the innate immune response and antiviral cytosolic DNA sensing. It is a critical regulator of the innate immune response and survival during sepsis by maintaining redox homeostasis and restraint of the dysregulation of proinflammatory signaling pathways like MyD88-dependent and -independent and TNF-alpha signaling (By similarity). Suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription and the induction of IL6 (By similarity). Binds to the proximity of proinflammatory genes in macrophages and inhibits RNA Pol II recruitment. The inhibition is independent of the NRF2-binding motif and reactive oxygen species level (By similarity). Represses antiviral cytosolic DNA sensing by suppressing the expression of the adapter protein STING1 and decreasing responsiveness to STING1 agonists while increasing susceptibility to infection with DNA viruses. Once activated, limits the release of pro-inflammatory cytokines in response to human coronavirus SARS-CoV-2 infection and to virus-derived ligands through a mechanism that involves inhibition of IRF3 dimerization. Also inhibits both SARS-CoV-2 replication, as well as the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism .
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Gene ID 4780
Uniprot ID
NF2L2_HUMAN
HGNC ID
HGNC:7782
Ensembl Gene ID
ENSG00000116044
KEGG ID
hsa:4780
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
NFE2L2 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
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Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LX2 cell line Homo sapiens
Treatment: shMETTL3 LX2 cells
Control: shLuc LX2 cells
 GSE207909
Regulation
logFC: -1.10E+00
p-value: 4.72E-06
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nuclear factor erythroid 2-related factor 2 (NFE2L2) signaling pathway.
Target Regulation Up regulation
Responsed Disease Diseases of the urinary system ICD-11: GC2Z
 Disease Info 
Responsed Drug Colistin Approved
 Drug Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nuclear factor erythroid 2-related factor 2 (NFE2L2)-mediated antioxidant pathway, and increased apoptosis in testes. DEHP is a common environmental endocrine disrupting chemical that induces male reproductive disorders. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2.
Target Regulation Up regulation
Responsed Disease Male reproductive disorders ICD-11: VV5Z
 Disease Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model Exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage.
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nuclear factor erythroid 2-related factor 2 (NFE2L2)-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Target Regulation Down regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Chemical carcinogenesis - reactive oxygen species hsa05208
Cell cycle hsa04110
Cell Process Biological regulation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
GLC-82 Endocervical adenocarcinoma Homo sapiens CVCL_3371
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HEK293T Normal Homo sapiens CVCL_0063
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H838 Lung adenocarcinoma Homo sapiens CVCL_1594
SPC-A1 Endocervical adenocarcinoma Homo sapiens CVCL_6955
In-vivo Model Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
YTH domain-containing protein 2 (YTHDC2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nuclear factor erythroid 2-related factor 2 (NFE2L2)-mediated antioxidant pathway, and increased apoptosis in testes. DEHP is a common environmental endocrine disrupting chemical that induces male reproductive disorders. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2.
Responsed Disease Male reproductive disorders ICD-11: VV5Z
 Disease Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model Exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nuclear factor erythroid 2-related factor 2 (NFE2L2)-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Chemical carcinogenesis - reactive oxygen species hsa05208
Cell cycle hsa04110
Cell Process Biological regulation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
GLC-82 Endocervical adenocarcinoma Homo sapiens CVCL_3371
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HEK293T Normal Homo sapiens CVCL_0063
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H838 Lung adenocarcinoma Homo sapiens CVCL_1594
SPC-A1 Endocervical adenocarcinoma Homo sapiens CVCL_6955
In-vivo Model Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Diseases of the urinary system [ICD-11: GC2Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nuclear factor erythroid 2-related factor 2 (NFE2L2) signaling pathway.
Responsed Disease Diseases of the urinary system [ICD-11: GC2Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Colistin Approved
 Drug Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
Male reproductive disorders [ICD-11: VV5Z]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nuclear factor erythroid 2-related factor 2 (NFE2L2)-mediated antioxidant pathway, and increased apoptosis in testes. DEHP is a common environmental endocrine disrupting chemical that induces male reproductive disorders. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2.
Responsed Disease Male reproductive disorders [ICD-11: VV5Z]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model Exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nuclear factor erythroid 2-related factor 2 (NFE2L2)-mediated antioxidant pathway, and increased apoptosis in testes. DEHP is a common environmental endocrine disrupting chemical that induces male reproductive disorders. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2.
Responsed Disease Male reproductive disorders [ICD-11: VV5Z]
Target Regulator YTH domain-containing protein 2 (YTHDC2) READER
 Regulator Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model Exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage.
Cisplatin [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nuclear factor erythroid 2-related factor 2 (NFE2L2)-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Chemical carcinogenesis - reactive oxygen species hsa05208
Cell cycle hsa04110
Cell Process Biological regulation
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
GLC-82 Endocervical adenocarcinoma Homo sapiens CVCL_3371
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HEK293T Normal Homo sapiens CVCL_0063
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H838 Lung adenocarcinoma Homo sapiens CVCL_1594
SPC-A1 Endocervical adenocarcinoma Homo sapiens CVCL_6955
In-vivo Model Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 106 p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Colistin [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nuclear factor erythroid 2-related factor 2 (NFE2L2) signaling pathway.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Diseases of the urinary system ICD-11: GC2Z
 Disease Info 
Cell Process Oxidative stress
Cell apoptosis
In-vivo Model The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
References
Ref 1 METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nrf2 signaling pathway. Toxicology. 2021 Oct;462:152961. doi: 10.1016/j.tox.2021.152961. Epub 2021 Sep 21.
Ref 2 Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl) phthalate-induced prepubertal testicular injury. Environ Pollut. 2020 Apr;259:113911. doi: 10.1016/j.envpol.2020.113911. Epub 2020 Jan 6.
Ref 3 YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. Nat Commun. 2019 Oct 25;10(1):4892. doi: 10.1038/s41467-019-12801-6.