m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00351)
Target Name Neurogenic locus notch homolog protein 1 (NOTCH1)
Synonyms
Notch 1; hN1; Translocation-associated notch protein TAN-1; NEXT; NICD; TAN1
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Gene Name NOTCH1
Chromosomal Location 9q34.3
Family NOTCH family
Function
Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).
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Gene ID 4851
Uniprot ID
NOTC1_HUMAN
HGNC ID
HGNC:7881
Ensembl Gene ID
ENSG00000148400
KEGG ID
hsa:4851
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
NOTCH1 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).
Browse Regulator
Browse Disease
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by FTO
Cell Line 253J cell line Homo sapiens
Treatment: siFTO 253J cells
Control: 253J cells
 GSE150239
Regulation
logFC: 6.94E-01
p-value: 5.11E-07
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 In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of MALAT1 and Neurogenic locus notch homolog protein 1 (NOTCH1) transcripts, and at 3' UTR of CSNK2A2 and ITGA6 transcripts, responding to the overexpression of FTO. SFPQ could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.
Target Regulation Down regulation
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Pathway Response Notch signaling pathway hsa04330
Cell Process Cell proliferation
Cell invasion
Cell apoptosis
In-vitro Model HT-1197 Recurrent bladder carcinoma Homo sapiens CVCL_1291
HT-1376 Bladder carcinoma Homo sapiens CVCL_1292
In-vivo Model BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 106 HT-1197 cells in control group or FTO plasmid group, respectively.
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line MDA-MB-231 Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells
Control: MDA-MB-231 cells
 GSE81164
Regulation
logFC: -8.37E-01
p-value: 6.43E-03
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 [2]
Response Summary Mettl14 and m6A modification participate in the RNA stability of Neurogenic locus notch homolog protein 1 (NOTCH1) mRNA. Notch1 plays an essential role in bladder tumorigenesis and bladder TIC self-renewal.
Target Regulation Down regulation
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Cell Process Cell proliferation
Self-renewal
Cell metastasis
In-vitro Model Primary bladder cancer cells (Obtained from bladder cancer patients)
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: -6.68E-01
p-value: 1.32E-12
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 [3]
Response Summary METTL3-catalyzed m6A modification promotes Neurogenic locus notch homolog protein 1 (NOTCH1) expression and the activation of the Notch signaling pathway. Forced activation of Notch signaling pathway successfully rescues the growth, migration, and invasion capacities of METTL3-depleted ESCC cells.
Target Regulation Up regulation
Responsed Disease Esophageal squamous cell carcinoma ICD-11: 2B70.1
 Disease Info 
Pathway Response Notch signaling pathway hsa04330
Cell Process Cell migration
Cell invasion
In-vitro Model TE-9 Esophageal squamous cell carcinoma Homo sapiens CVCL_1767
KYSE-30 Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
In-vivo Model For induction of ESCC, 4-week-old mice were treated with drinking water containing 50 ug/mL 4NQO (Sigma-Aldrich, USA) for 16 weeks and then given normal drinking water for another 4-5 weeks. Cre was activated by the intraperitoneal injection of tamoxifen (Sigma-Aldrich, USA) at a dose of 9 mg per 40 g body weight every other day for a total of three injections. For tumor measurement, mice were sacrificed, and the esophagus was dissected immediately. The surface areas of tumors were measured as described previously.
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2
Cell Line Testis Mus musculus
Treatment: YTHDF2 knockout mice testis
Control: Mice testis
 GSE147574
Regulation
logFC: 1.06E+00
p-value: 8.73E-04
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 [4]
Response Summary YTHDF2 inhibits Notch signaling by downregulating the Neurogenic locus notch homolog protein 1 (NOTCH1), HES1, and HES5 mRNA levels.
Target Regulation Down regulation
Pathway Response Notch signaling pathway hsa04330
Cell Process Extracellular stress
Cell apoptosis
In-vitro Model HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
Jurkat T acute lymphoblastic leukemia Homo sapiens CVCL_0065
Bladder cancer [ICD-11: 2C94]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary In bladder cancer, the changes in m6A methylation level mainly appeared at 5' untranslated region (5' UTR) of MALAT1 and Neurogenic locus notch homolog protein 1 (NOTCH1) transcripts, and at 3' UTR of CSNK2A2 and ITGA6 transcripts, responding to the overexpression of FTO. SFPQ could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Notch signaling pathway hsa04330
Cell Process Cell proliferation
Cell invasion
Cell apoptosis
In-vitro Model HT-1197 Recurrent bladder carcinoma Homo sapiens CVCL_1291
HT-1376 Bladder carcinoma Homo sapiens CVCL_1292
In-vivo Model BALB/cnu/nu mice (4-5 weeks old) were used for the xenograft experiment. The mice were randomly divided into 2 groups (n = 6 for each group) and injected with 5 × 106 HT-1197 cells in control group or FTO plasmid group, respectively.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary Mettl14 and m6A modification participate in the RNA stability of Neurogenic locus notch homolog protein 1 (NOTCH1) mRNA. Notch1 plays an essential role in bladder tumorigenesis and bladder TIC self-renewal.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Cell Process Cell proliferation
Self-renewal
Cell metastasis
In-vitro Model Primary bladder cancer cells (Obtained from bladder cancer patients)
Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3-catalyzed m6A modification promotes Neurogenic locus notch homolog protein 1 (NOTCH1) expression and the activation of the Notch signaling pathway. Forced activation of Notch signaling pathway successfully rescues the growth, migration, and invasion capacities of METTL3-depleted ESCC cells.
Responsed Disease Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Notch signaling pathway hsa04330
Cell Process Cell migration
Cell invasion
In-vitro Model TE-9 Esophageal squamous cell carcinoma Homo sapiens CVCL_1767
KYSE-30 Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
In-vivo Model For induction of ESCC, 4-week-old mice were treated with drinking water containing 50 ug/mL 4NQO (Sigma-Aldrich, USA) for 16 weeks and then given normal drinking water for another 4-5 weeks. Cre was activated by the intraperitoneal injection of tamoxifen (Sigma-Aldrich, USA) at a dose of 9 mg per 40 g body weight every other day for a total of three injections. For tumor measurement, mice were sacrificed, and the esophagus was dissected immediately. The surface areas of tumors were measured as described previously.
References
Ref 1 The tumor-suppressive effects of alpha-ketoglutarate-dependent dioxygenase FTO via N6-methyladenosine RNA methylation on bladder cancer patients. Bioengineered. 2021 Dec;12(1):5323-5333. doi: 10.1080/21655979.2021.1964893.
Ref 2 Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N(6)-methyladenosine of Notch1. Mol Cancer. 2019 Nov 25;18(1):168. doi: 10.1186/s12943-019-1084-1.
Ref 3 METTL3-mediated m(6)A mRNA modification promotes esophageal cancer initiation and progression via Notch signaling pathway. Mol Ther Nucleic Acids. 2021 Jul 21;26:333-346. doi: 10.1016/j.omtn.2021.07.007. eCollection 2021 Dec 3.
Ref 4 YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1. Int J Biol Sci. 2021 Aug 28;17(14):3776-3785. doi: 10.7150/ijbs.61573. eCollection 2021.