General Information of the m6A Target Gene (ID: M6ATAR00325)
Target Name Hepatocyte growth factor receptor (c-Met/MET)
Synonyms
HGF receptor; HGF/SF receptor; Proto-oncogene c-Met; Scatter factor receptor; SF receptor; Tyrosine-protein kinase Met
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Gene Name MET
Chromosomal Location 7q31
Family protein kinase superfamily; Tyr protein kinase family
Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity); (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells.
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Gene ID 4233
Uniprot ID
MET_HUMAN
HGNC ID
HGNC:7029
Ensembl Gene ID
ENSG00000105976
KEGG ID
hsa:4233
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
MET 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]
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: 6.42E-01
p-value: 3.45E-17
More Results Click to View More RNA-seq Results
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
Responsed Drug Crizotinib Approved
Pathway Response EGFR tyrosine kinase inhibitor resistance hsa01521
In-vitro Model HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H661 Lung large cell carcinoma Homo sapiens CVCL_1577
NCI-H596 Lung adenosquamous carcinoma Homo sapiens CVCL_1571
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1395 Lung adenocarcinoma Homo sapiens CVCL_1467
EBC-1 Lung squamous cell carcinoma Homo sapiens CVCL_2891
Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 combines with Hepatocyte growth factor receptor (c-Met/MET) and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells.
Target Regulation Up regulation
Responsed Disease Lung cancer ICD-11: 2C25
Responsed Drug Gefitinib Approved
Pathway Response PI3K-Akt signaling pathway hsa04151
In-vitro Model PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H3255 Lung adenocarcinoma Homo sapiens CVCL_6831
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3-mediated m6A RNA methylation modulates uveal melanoma cell proliferation, migration, and invasion by targeting Hepatocyte growth factor receptor (c-Met/MET). Cycloleucine (Cyc) was used to block m6 A methylation in UM cells.
Target Regulation Up regulation
Responsed Disease Melanoma of uvea ICD-11: 2D0Y
Pathway Response Cell cycle hsa04110
Cell Process Cell proliferation
Cell migration
Cell invasion
Arrest cell cycle at G1 phase
In-vitro Model M17 (Neuroblastoma cells)
M21 Melanoma Homo sapiens CVCL_D031
M23 Cutaneous melanoma Homo sapiens CVCL_RT32
SP-6.5 Uveal melanoma Homo sapiens CVCL_7997
Wilms tumor 1-associating protein (WTAP) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by WTAP
Cell Line mouse embryonic stem cells Mus musculus
Treatment: WTAP-/- ESCs
Control: Wild type ESCs
GSE145309
Regulation
logFC: -2.39E+00
p-value: 1.81E-38
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 Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
Responsed Drug Crizotinib Approved
Pathway Response EGFR tyrosine kinase inhibitor resistance hsa01521
In-vitro Model HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H661 Lung large cell carcinoma Homo sapiens CVCL_1577
NCI-H596 Lung adenosquamous carcinoma Homo sapiens CVCL_1571
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1395 Lung adenocarcinoma Homo sapiens CVCL_1467
EBC-1 Lung squamous cell carcinoma Homo sapiens CVCL_2891
Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Lung cancer [ICD-11: 2C25]
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Responsed Drug Crizotinib Approved
Pathway Response EGFR tyrosine kinase inhibitor resistance hsa01521
In-vitro Model HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H661 Lung large cell carcinoma Homo sapiens CVCL_1577
NCI-H596 Lung adenosquamous carcinoma Homo sapiens CVCL_1571
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1395 Lung adenocarcinoma Homo sapiens CVCL_1467
EBC-1 Lung squamous cell carcinoma Homo sapiens CVCL_2891
Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 combines with Hepatocyte growth factor receptor (c-Met/MET) and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells.
Responsed Disease Lung cancer [ICD-11: 2C25]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Responsed Drug Gefitinib Approved
Pathway Response PI3K-Akt signaling pathway hsa04151
In-vitro Model PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H3255 Lung adenocarcinoma Homo sapiens CVCL_6831
Experiment 3 Reporting the m6A-centered Disease Response [1]
Response Summary Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Wilms tumor 1-associating protein (WTAP) WRITER
Target Regulation Up regulation
Responsed Drug Crizotinib Approved
Pathway Response EGFR tyrosine kinase inhibitor resistance hsa01521
In-vitro Model HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H661 Lung large cell carcinoma Homo sapiens CVCL_1577
NCI-H596 Lung adenosquamous carcinoma Homo sapiens CVCL_1571
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1395 Lung adenocarcinoma Homo sapiens CVCL_1467
EBC-1 Lung squamous cell carcinoma Homo sapiens CVCL_2891
Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Melanoma of uvea [ICD-11: 2D0Y]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3-mediated m6A RNA methylation modulates uveal melanoma cell proliferation, migration, and invasion by targeting Hepatocyte growth factor receptor (c-Met/MET). Cycloleucine (Cyc) was used to block m6 A methylation in UM cells.
Responsed Disease Melanoma of uvea [ICD-11: 2D0Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Cell proliferation
Cell migration
Cell invasion
Arrest cell cycle at G1 phase
In-vitro Model M17 (Neuroblastoma cells)
M21 Melanoma Homo sapiens CVCL_D031
M23 Cutaneous melanoma Homo sapiens CVCL_RT32
SP-6.5 Uveal melanoma Homo sapiens CVCL_7997
Crizotinib [Approved]
In total 2 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
Pathway Response EGFR tyrosine kinase inhibitor resistance hsa01521
In-vitro Model HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H661 Lung large cell carcinoma Homo sapiens CVCL_1577
NCI-H596 Lung adenosquamous carcinoma Homo sapiens CVCL_1571
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1395 Lung adenocarcinoma Homo sapiens CVCL_1467
EBC-1 Lung squamous cell carcinoma Homo sapiens CVCL_2891
Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Experiment 2 Reporting the m6A-centered Drug Response [1]
Response Summary Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Target Regulator Wilms tumor 1-associating protein (WTAP) WRITER
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
Pathway Response EGFR tyrosine kinase inhibitor resistance hsa01521
In-vitro Model HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H661 Lung large cell carcinoma Homo sapiens CVCL_1577
NCI-H596 Lung adenosquamous carcinoma Homo sapiens CVCL_1571
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H358 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1395 Lung adenocarcinoma Homo sapiens CVCL_1467
EBC-1 Lung squamous cell carcinoma Homo sapiens CVCL_2891
Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model HCC827 (3×106) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm3 on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Gefitinib [Approved]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary METTL3 combines with Hepatocyte growth factor receptor (c-Met/MET) and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Responsed Disease Lung cancer ICD-11: 2C25
Pathway Response PI3K-Akt signaling pathway hsa04151
In-vitro Model PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H3255 Lung adenocarcinoma Homo sapiens CVCL_6831
References
Ref 1 Chidamide increases the sensitivity of Non-small Cell Lung Cancer to Crizotinib by decreasing c-MET mRNA methylation. Int J Biol Sci. 2020 Jul 19;16(14):2595-2611. doi: 10.7150/ijbs.45886. eCollection 2020.
Ref 2 RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma. J Cell Mol Med. 2021 Mar;25(5):2418-2425. doi: 10.1111/jcmm.16114. Epub 2021 Jan 24.
Ref 3 RNA m(6) A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c-Met. J Cell Physiol. 2020 Oct;235(10):7107-7119. doi: 10.1002/jcp.29608. Epub 2020 Feb 4.