m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00211)
Target Name Cyclin-dependent kinase 4 (CDK4)
Synonyms
Cell division protein kinase 4; PSK-J3
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Gene Name CDK4
Chromosomal Location 12q14.1
Family protein kinase superfamily; CMGC Ser/Thr protein kinase family; CDC2/CDKX subfamily
Function
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.
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Gene ID 1019
Uniprot ID
CDK4_HUMAN
HGNC ID
HGNC:1773
Ensembl Gene ID
ENSG00000135446
KEGG ID
hsa:1019
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
CDK4 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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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: -1.19E+00
p-value: 3.49E-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 [1]
Response Summary GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, Cyclin-dependent kinase 4 (CDK4), EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Cell Process Cell apoptosis
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
HBE (Human bronchial epithelial cell line)
LTEP-a2 Endocervical adenocarcinoma Homo sapiens CVCL_6929
SK-MES-1 Lung squamous cell carcinoma Homo sapiens CVCL_0630
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) [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 DMDRMR is a protumorigenic lncRNA that mediates the stabilization of IGF2BP3 targets in an m6A-dependent manner in clear cell renal cell carcinoma. IGF2BP3 and DMDRMR cooperate to play oncogenic roles. IGF2BP3 cooperates with DMDRMR to regulate Cyclin-dependent kinase 4 (CDK4) by enhancing mRNA stability.
Target Regulation Up regulation
Responsed Disease Renal cell carcinoma of kidney ICD-11: 2C90.0
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process Accelerating the G1-S transition
Cell invasion and metastasis
In-vitro Model 769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
In-vivo Model Stable DMDRMR knockdown (KD) and control cell lines were injected subcutaneously (s.c.; 1 × 107 cells/inoculum) into the flanks of recipient NOD/SCID/IL2Rγ-null (NSG) mice.
Protein virilizer homolog (VIRMA) [WRITER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, Cyclin-dependent kinase 4 (CDK4), EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Cell Process Cell apoptosis
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
HBE (Human bronchial epithelial cell line)
LTEP-a2 Endocervical adenocarcinoma Homo sapiens CVCL_6929
SK-MES-1 Lung squamous cell carcinoma Homo sapiens CVCL_0630
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, Cyclin-dependent kinase 4 (CDK4), p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-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 Up 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.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, Cyclin-dependent kinase 4 (CDK4), EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease Lung cancer [ICD-11: 2C25]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
 Regulator Info 
Cell Process Cell apoptosis
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
HBE (Human bronchial epithelial cell line)
LTEP-a2 Endocervical adenocarcinoma Homo sapiens CVCL_6929
SK-MES-1 Lung squamous cell carcinoma Homo sapiens CVCL_0630
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary GSEA revealed that KIAA1429, METTL3, and IGF2BP1 were significantly related to multiple biological behaviors, including proliferation, apoptosis, metastasis, energy metabolism, drug resistance, and recurrence, and that KIAA1429 and IGF2BP1 had potential target genes, including E2F3, WTAP, CCND1, Cyclin-dependent kinase 4 (CDK4), EGR2, YBX1, and TLX, which were associated with lung cancers.
Responsed Disease Lung cancer [ICD-11: 2C25]
Target Regulator Protein virilizer homolog (VIRMA) WRITER
 Regulator Info 
Cell Process Cell apoptosis
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
HBE (Human bronchial epithelial cell line)
LTEP-a2 Endocervical adenocarcinoma Homo sapiens CVCL_6929
SK-MES-1 Lung squamous cell carcinoma Homo sapiens CVCL_0630
Experiment 3 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, Cyclin-dependent kinase 4 (CDK4), p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-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 Up 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.
Renal cell carcinoma [ICD-11: 2C90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary DMDRMR is a protumorigenic lncRNA that mediates the stabilization of IGF2BP3 targets in an m6A-dependent manner in clear cell renal cell carcinoma. IGF2BP3 and DMDRMR cooperate to play oncogenic roles. IGF2BP3 cooperates with DMDRMR to regulate Cyclin-dependent kinase 4 (CDK4) by enhancing mRNA stability.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Accelerating the G1-S transition
Cell invasion and metastasis
In-vitro Model 769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
In-vivo Model Stable DMDRMR knockdown (KD) and control cell lines were injected subcutaneously (s.c.; 1 × 107 cells/inoculum) into the flanks of recipient NOD/SCID/IL2Rγ-null (NSG) mice.
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, Cyclin-dependent kinase 4 (CDK4), p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-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 Up 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.
References
Ref 1 Identification of pathology-specific regulators of m(6)A RNA modification to optimize lung cancer management in the context of predictive, preventive, and personalized medicine. EPMA J. 2020 Jul 29;11(3):485-504. doi: 10.1007/s13167-020-00220-3. eCollection 2020 Sep.
Ref 2 DMDRMR-Mediated Regulation of m(6)A-Modified CDK4 by m(6)A Reader IGF2BP3 Drives ccRCC Progression. Cancer Res. 2021 Feb 15;81(4):923-934. doi: 10.1158/0008-5472.CAN-20-1619. Epub 2020 Dec 8.
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.