m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00249)
Target Name Histone-lysine N-methyltransferase EZH2 (EZH2)
Synonyms
ENX-1; Enhancer of zeste homolog 2; Lysine N-methyltransferase 6; KMT6
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Gene Name EZH2
Chromosomal Location 7q36.1
Family class V-like SAM-binding methyltransferase superfamily; Histone-lysine methyltransferase family; EZ subfamily
Function
Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2. Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription.
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Gene ID 2146
Uniprot ID
EZH2_HUMAN
HGNC ID
HGNC:3527
Ensembl Gene ID
ENSG00000106462
KEGG ID
hsa:2146
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
EZH2 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
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: -1.23E+00
p-value: 1.10E-12
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between EZH2 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 2.01E+00 GSE60213
In total 4 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 was highly expressed in nasopharyngeal carcinoma tissues, which inhibited Histone-lysine N-methyltransferase EZH2 (EZH2) expression by mediating M6A modification of EZH2 mRNA.
Target Regulation Down regulation
Responsed Disease Nasopharyngeal carcinoma ICD-11: 2B6B
 Disease Info 
Cell Process Cell viability
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
C666-1 Nasopharyngeal carcinoma Homo sapiens CVCL_7949
SUNE1 Nasopharyngeal carcinoma Homo sapiens CVCL_6946
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on Histone-lysine N-methyltransferase EZH2 (EZH2) mRNA and thus inhibits the malignant progression of lung cancer.
Target Regulation Up regulation
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Cell Process Epithelial-mesenchymal transition
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 is upregulated in Breast Cancer. It could regulate the protein level of Histone-lysine N-methyltransferase EZH2 (EZH2) through m6A modification to promote EMT and metastasis in BCa cells, thereafter aggravating the progression of BCa.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Adherens junction hsa04520
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3 promotes inflammation and cell apoptosis in a pediatric pneumonia model by regulating Histone-lysine N-methyltransferase EZH2 (EZH2).
Target Regulation Up regulation
Responsed Disease Congenital pneumonia ICD-11: KB24
 Disease Info 
Pathway Response JAK-STAT signaling pathway hsa04630
Cell Process Inflammation
In-vitro Model HPBM (Human Peripheral Blood Monocytes)
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by IGF2BP1
Cell Line PANC-1 cell line Homo sapiens
Treatment: siIGF2BP1 PANC-1 cells
Control: siControl PANC-1 cells
 GSE161087
Regulation
logFC: -1.26E+00
p-value: 4.20E-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 [5]
Response Summary This data identify IGF2BP1 as an important driver of tumor progression in NEN, and indicate that disruption of the IGF2BP1-Myc-Histone-lysine N-methyltransferase EZH2 (EZH2) axis represents a promising approach for targeted therapy of neuroendocrine neoplasms.
Target Regulation Up regulation
Responsed Disease Neuroendocrine neoplasms ICD-11: 2D4Y
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process Increase in G1 and sub-G1 phases
In-vitro Model NCI-H727 Lung carcinoid tumor Homo sapiens CVCL_1584
COLO 320DM Colon adenocarcinoma Homo sapiens CVCL_0219
In-vivo Model RIP1-Tag2 mice were purchased from NCI Mouse Repository (Bethesda, Rockville, MD, USA) and maintained in a C57BL/6N background.
Nasopharyngeal carcinoma [ICD-11: 2B6B]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 was highly expressed in nasopharyngeal carcinoma tissues, which inhibited Histone-lysine N-methyltransferase EZH2 (EZH2) expression by mediating M6A modification of EZH2 mRNA.
Responsed Disease Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Cell Process Cell viability
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
C666-1 Nasopharyngeal carcinoma Homo sapiens CVCL_7949
SUNE1 Nasopharyngeal carcinoma Homo sapiens CVCL_6946
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on Histone-lysine N-methyltransferase EZH2 (EZH2) mRNA and thus inhibits the malignant progression of lung cancer.
Responsed Disease Lung cancer [ICD-11: 2C25]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Epithelial-mesenchymal transition
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 is upregulated in Breast Cancer. It could regulate the protein level of Histone-lysine N-methyltransferase EZH2 (EZH2) through m6A modification to promote EMT and metastasis in BCa cells, thereafter aggravating the progression of BCa.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Adherens junction hsa04520
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
Neuroendocrine neoplasms [ICD-11: 2D4Y]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary This data identify IGF2BP1 as an important driver of tumor progression in NEN, and indicate that disruption of the IGF2BP1-Myc-Histone-lysine N-methyltransferase EZH2 (EZH2) axis represents a promising approach for targeted therapy of neuroendocrine neoplasms.
Responsed Disease Neuroendocrine neoplasms [ICD-11: 2D4Y]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Increase in G1 and sub-G1 phases
In-vitro Model NCI-H727 Lung carcinoid tumor Homo sapiens CVCL_1584
COLO 320DM Colon adenocarcinoma Homo sapiens CVCL_0219
In-vivo Model RIP1-Tag2 mice were purchased from NCI Mouse Repository (Bethesda, Rockville, MD, USA) and maintained in a C57BL/6N background.
Congenital pneumonia [ICD-11: KB24]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3 promotes inflammation and cell apoptosis in a pediatric pneumonia model by regulating Histone-lysine N-methyltransferase EZH2 (EZH2).
Responsed Disease Congenital pneumonia [ICD-11: KB24]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response JAK-STAT signaling pathway hsa04630
Cell Process Inflammation
In-vitro Model HPBM (Human Peripheral Blood Monocytes)
References
Ref 1 METTL3 promotes the progression of nasopharyngeal carcinoma through mediating M6A modification of EZH2. Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4328-4336. doi: 10.26355/eurrev_202004_21014.
Ref 2 Simvastatin is beneficial to lung cancer progression by inducing METTL3-induced m6A modification on EZH2 mRNA. Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4263-4270. doi: 10.26355/eurrev_202004_21006.
Ref 3 METTL3 Accelerates Breast Cancer Progression via Regulating EZH2 m(6)A Modification. J Healthc Eng. 2022 Mar 29;2022:5794422. doi: 10.1155/2022/5794422. eCollection 2022.
Ref 4 METTL3 promotes inflammation and cell apoptosis in a pediatric pneumonia model by regulating EZH2. Allergol Immunopathol (Madr). 2021 Sep 1;49(5):49-56. doi: 10.15586/aei.v49i5.445. eCollection 2021.
Ref 5 IGF2BP1 Promotes Proliferation of Neuroendocrine Neoplasms by Post-Transcriptional Enhancement of EZH2. Cancers (Basel). 2022 Apr 24;14(9):2121. doi: 10.3390/cancers14092121.