m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00214)
Target Name Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27)
Synonyms
Cyclin-dependent kinase inhibitor p27; p27Kip1; KIP1
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Gene Name CDKN1B
Chromosomal Location 12p13.1
Family CDI family
Function
Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.
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Gene ID 1027
Uniprot ID
CDN1B_HUMAN
HGNC ID
HGNC:1785
Ensembl Gene ID
ENSG00000111276
KEGG ID
hsa:1027
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
CDKN1B 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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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 [1]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, Cyclin-dependent kinase inhibitor 1B (CDKN1B/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 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 family protein 2 (YTHDF2) [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 The role of YTHDF2 in tumourigenesis and cisplatin-desensitising function by promoting the degradation of Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27) mRNA in an m6 A-dependent manner. YTHDF2 exhibits tumour oncogenic and cisplatin-desensitising properties, which offer insight into the development of novel combination therapeutic strategies for intrahepatic cholangiocarcinoma.
Target Regulation Down regulation
Responsed Disease Intrahepatic cholangiocarcinoma ICD-11: 2C12.10
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Cell cycle hsa04110
Cell Process Cell proliferation
Arrest cell cycle at G0/G1 phase
In-vitro Model HuCC-T1 Intrahepatic cholangiocarcinoma Homo sapiens CVCL_0324
RBE Intrahepatic cholangiocarcinoma Homo sapiens CVCL_4896
HCCC-9810 (The intrahepatic cholangiocarcinoma cell lines (HCCC-9810) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
HIBEC (The normal intrahepatic bile duct cell line (HIBEC) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
In-vivo Model For tumour xenograft models, 1 × 107 HuCC-T1 cells in knockdown group or control group were implanted into the right flank of 5-week-old female nude mice. The volumes of tumour were recorded every 4 days by calliper. The volumes were calculated as length × width2/2. For patient-derived xenograft (PDX) model (PDX0075), ICC tissues from a patient, who relapsed in 6 months after R0 resection and subsequent chemotherapy with cisplatin and gemcitabine, were diced into 3 mm3 pieces and transplanted subcutaneously into the right flank of 5-week-old female B-NDG mice.
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary The role of YTHDF2 in tumourigenesis and cisplatin-desensitising function by promoting the degradation of Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27) mRNA in an m6 A-dependent manner. YTHDF2 exhibits tumour oncogenic and cisplatin-desensitising properties, which offer insight into the development of novel combination therapeutic strategies for intrahepatic cholangiocarcinoma.
Responsed Disease Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Cell cycle hsa04110
Cell Process Cell proliferation
Arrest cell cycle at G0/G1 phase
In-vitro Model HuCC-T1 Intrahepatic cholangiocarcinoma Homo sapiens CVCL_0324
RBE Intrahepatic cholangiocarcinoma Homo sapiens CVCL_4896
HCCC-9810 (The intrahepatic cholangiocarcinoma cell lines (HCCC-9810) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
HIBEC (The normal intrahepatic bile duct cell line (HIBEC) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
In-vivo Model For tumour xenograft models, 1 × 107 HuCC-T1 cells in knockdown group or control group were implanted into the right flank of 5-week-old female nude mice. The volumes of tumour were recorded every 4 days by calliper. The volumes were calculated as length × width2/2. For patient-derived xenograft (PDX) model (PDX0075), ICC tissues from a patient, who relapsed in 6 months after R0 resection and subsequent chemotherapy with cisplatin and gemcitabine, were diced into 3 mm3 pieces and transplanted subcutaneously into the right flank of 5-week-old female B-NDG mice.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, Cyclin-dependent kinase inhibitor 1B (CDKN1B/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 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.
Cisplatin [Approved]
 Drug Info 
In total 2 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, Cyclin-dependent kinase inhibitor 1B (CDKN1B/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 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.
Experiment 2 Reporting the m6A-centered Drug Response [2]
Response Summary The role of YTHDF2 in tumourigenesis and cisplatin-desensitising function by promoting the degradation of Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27) mRNA in an m6 A-dependent manner. YTHDF2 exhibits tumour oncogenic and cisplatin-desensitising properties, which offer insight into the development of novel combination therapeutic strategies for intrahepatic cholangiocarcinoma.
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Intrahepatic cholangiocarcinoma ICD-11: 2C12.10
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process Cell proliferation
Arrest cell cycle at G0/G1 phase
In-vitro Model HuCC-T1 Intrahepatic cholangiocarcinoma Homo sapiens CVCL_0324
RBE Intrahepatic cholangiocarcinoma Homo sapiens CVCL_4896
HCCC-9810 (The intrahepatic cholangiocarcinoma cell lines (HCCC-9810) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
HIBEC (The normal intrahepatic bile duct cell line (HIBEC) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
In-vivo Model For tumour xenograft models, 1 × 107 HuCC-T1 cells in knockdown group or control group were implanted into the right flank of 5-week-old female nude mice. The volumes of tumour were recorded every 4 days by calliper. The volumes were calculated as length × width2/2. For patient-derived xenograft (PDX) model (PDX0075), ICC tissues from a patient, who relapsed in 6 months after R0 resection and subsequent chemotherapy with cisplatin and gemcitabine, were diced into 3 mm3 pieces and transplanted subcutaneously into the right flank of 5-week-old female B-NDG mice.
References
Ref 1 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.
Ref 2 YTHDF2 promotes intrahepatic cholangiocarcinoma progression and desensitises cisplatin treatment by increasing CDKN1B mRNA degradation. Clin Transl Med. 2022 Jun;12(6):e848. doi: 10.1002/ctm2.848.