m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00206)
Target Name G1/S-specific cyclin-D1 (CCND1)
Synonyms
B-cell lymphoma 1 protein; BCL-1; BCL-1 oncogene; PRAD1 oncogene; BCL1; PRAD1
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Gene Name CCND1
Chromosomal Location 11q13.3
Family cyclin family; Cyclin D subfamily
Function
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex 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 substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner.
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Gene ID 595
Uniprot ID
CCND1_HUMAN
HGNC ID
HGNC:1582
Ensembl Gene ID
ENSG00000110092
KEGG ID
hsa:595
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
CCND1 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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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 NB4 cell line Homo sapiens
Treatment: FTO inhibition NB4 cells
Control: NB4 cells
 GSE103495
Regulation
logFC: -7.40E-01
p-value: 1.34E-03
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary FTO regulates myoblast proliferation by controlling G1/S-specific cyclin-D1 (CCND1) expression in an m6A-YTHDF2-dependent manner.
Target Regulation Up regulation
Cell Process Cell proliferation
Cell apoptosis
In-vitro Model GPM (Goat primary myoblasts)
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of G1/S-specific cyclin-D1 (CCND1) and Cdk2(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.
Responsed Disease Obesity ICD-11: 5B81
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process Cell cycle
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LNCaP cell line Homo sapiens
Treatment: shMETTL3 LNCaP cells
Control: shControl LNCaP cells
 GSE147884
Regulation
logFC: -6.51E-01
p-value: 1.46E-104
More Results Click to View More RNA-seq Results
In total 4 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and G1/S-specific cyclin-D1 (CCND1).
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3 knockdown downregulated the phosphorylation levels of AKT and the expression of the downstream effector G1/S-specific cyclin-D1 (CCND1) in ovarian cancer.
Target Regulation Up regulation
Responsed Disease Ovarian cancer ICD-11: 2C73
 Disease Info 
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell cycle
Cell apoptosis
In-vitro Model OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through G1/S-specific cyclin-D1 (CCND1) targeting.
Target Regulation Down regulation
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
In-vitro Model SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
In-vivo Model Mice were divided into two groups (n = 4/group) randomly. 3×106 cells suspended in 200 uL PBS were administered via subcutaneous injection over the right flank region of nude mice. After the development of palpable tumors (average volume, 50 mm3), intratumoral injection of synthetic miR-193b, or negative control complexed with siPORT Amine transfection reagent (Ambion, USA) was given 6 times at a 4-day interval.
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Obesity is becoming a global problem. ZFP217 knockdown-induced adipogenesis inhibition was caused by G1/S-specific cyclin-D1 (CCND1), which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner.
Target Regulation Up regulation
Responsed Disease Obesity ICD-11: 5B81
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process Mitotic clonal
Prolonged G1/S transition
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
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 GSC11 cell line Homo sapiens
Treatment: siYTHDF2 GSC11 cells
Control: siControl GSC11 cells
 GSE142825
Regulation
logFC: 1.13E+00
p-value: 1.41E-27
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 FTO regulates myoblast proliferation by controlling G1/S-specific cyclin-D1 (CCND1) expression in an m6A-YTHDF2-dependent manner.
Target Regulation Down regulation
Cell Process Cell proliferation
Cell apoptosis
In-vitro Model GPM (Goat primary myoblasts)
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Obesity is becoming a global problem. ZFP217 knockdown-induced adipogenesis inhibition was caused by G1/S-specific cyclin-D1 (CCND1), which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner.
Target Regulation Down regulation
Responsed Disease Obesity ICD-11: 5B81
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process Mitotic clonal
Prolonged G1/S transition
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of G1/S-specific cyclin-D1 (CCND1) and Cdk2(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.
Responsed Disease Obesity ICD-11: 5B81
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process Cell cycle
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [7]
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, G1/S-specific cyclin-D1 (CCND1), 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
Methyltransferase-like 16 (METTL16) [WRITER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [8]
Response Summary METTL16-mediated m6A methylation promotes proliferation of gastric cancer cells through enhancing G1/S-specific cyclin-D1 (CCND1) expression.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response Cell cycle hsa04110
Cell Process G1/S blocking
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model Xenograft mouse model was used to verify the tumorigenic effect of METTL16 in vivo. BALB/c nude mice (4 weeks old) were injected with METTL16 gene knock-down stable MGC803 GC cells (3 × 106 cells/mice, subcutaneous injection) or shNC control cells (3 × 106, subcutaneous injection), and the dose was 100 uL, with PBS as solvent. The tumour size was measured every 3-5 days. At the end of feeding (6 weeks after subcutaneous injection), the mice were killed and the tumours were extracted for histological analysis.
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 [7]
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, G1/S-specific cyclin-D1 (CCND1), 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 [9]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and G1/S-specific cyclin-D1 (CCND1), 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.
YTH domain-containing family protein 3 (YTHDF3) [READER]
 Regulator Info 
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [10]
Response Summary Dysfunction of Ythdf3 and Mettl3 results in the translational defect of G1/S-specific cyclin-D1 (CCND1). Ythdf3 and Mettl3 regulates HSCs by transmitting m6A RNA methylation on the 5'UTR of Ccnd1.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [10]
Response Summary Dysfunction of Ythdf3 and Mettl3 results in the translational defect of G1/S-specific cyclin-D1 (CCND1). Ythdf3 and Mettl3 regulates HSCs by transmitting m6A RNA methylation on the 5'UTR of Ccnd1.
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [8]
Response Summary METTL16-mediated m6A methylation promotes proliferation of gastric cancer cells through enhancing G1/S-specific cyclin-D1 (CCND1) expression.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 16 (METTL16) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process G1/S blocking
In-vitro Model SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model Xenograft mouse model was used to verify the tumorigenic effect of METTL16 in vivo. BALB/c nude mice (4 weeks old) were injected with METTL16 gene knock-down stable MGC803 GC cells (3 × 106 cells/mice, subcutaneous injection) or shNC control cells (3 × 106, subcutaneous injection), and the dose was 100 uL, with PBS as solvent. The tumour size was measured every 3-5 days. At the end of feeding (6 weeks after subcutaneous injection), the mice were killed and the tumours were extracted for histological analysis.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and G1/S-specific cyclin-D1 (CCND1).
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation
Cell migration
Cell invasion
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [7]
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, G1/S-specific cyclin-D1 (CCND1), 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 [7]
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, G1/S-specific cyclin-D1 (CCND1), 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 [9]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and G1/S-specific cyclin-D1 (CCND1), 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.
Ovarian cancer [ICD-11: 2C73]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3 knockdown downregulated the phosphorylation levels of AKT and the expression of the downstream effector G1/S-specific cyclin-D1 (CCND1) in ovarian cancer.
Responsed Disease Ovarian cancer [ICD-11: 2C73]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell cycle
Cell apoptosis
In-vitro Model OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
Cervical cancer [ICD-11: 2C77]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through G1/S-specific cyclin-D1 (CCND1) targeting.
Responsed Disease Cervical cancer [ICD-11: 2C77]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
In-vitro Model SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
In-vivo Model Mice were divided into two groups (n = 4/group) randomly. 3×106 cells suspended in 200 uL PBS were administered via subcutaneous injection over the right flank region of nude mice. After the development of palpable tumors (average volume, 50 mm3), intratumoral injection of synthetic miR-193b, or negative control complexed with siPORT Amine transfection reagent (Ambion, USA) was given 6 times at a 4-day interval.
Obesity [ICD-11: 5B81]
 Disease Info 
In total 4 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of G1/S-specific cyclin-D1 (CCND1) and Cdk2(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.
Responsed Disease Obesity [ICD-11: 5B81]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Pathway Response Cell cycle hsa04110
Cell Process Cell cycle
Experiment 2 Reporting the m6A-centered Disease Response [6]
Response Summary Obesity is becoming a global problem. ZFP217 knockdown-induced adipogenesis inhibition was caused by G1/S-specific cyclin-D1 (CCND1), which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner.
Responsed Disease Obesity [ICD-11: 5B81]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Mitotic clonal
Prolonged G1/S transition
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
Experiment 3 Reporting the m6A-centered Disease Response [6]
Response Summary Obesity is becoming a global problem. ZFP217 knockdown-induced adipogenesis inhibition was caused by G1/S-specific cyclin-D1 (CCND1), which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner.
Responsed Disease Obesity [ICD-11: 5B81]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Cell cycle hsa04110
Cell Process Mitotic clonal
Prolonged G1/S transition
In-vitro Model 3T3-L1 Normal Mus musculus CVCL_0123
Experiment 4 Reporting the m6A-centered Disease Response [2]
Response Summary Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of G1/S-specific cyclin-D1 (CCND1) and Cdk2(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.
Responsed Disease Obesity [ICD-11: 5B81]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Pathway Response Cell cycle hsa04110
Cell Process Cell cycle
Cisplatin [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [9]
Response Summary YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and G1/S-specific cyclin-D1 (CCND1), 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 FTO regulates myoblast proliferation by controlling CCND1 expression in an m(6)A-YTHDF2-dependent manner. Exp Cell Res. 2021 Apr 15;401(2):112524. doi: 10.1016/j.yexcr.2021.112524. Epub 2021 Feb 27.
Ref 2 Metformin combats obesity by targeting FTO in an m(6)A-YTHDF2-dependent manner. J Drug Target. 2022 May 9:1-9. doi: 10.1080/1061186X.2022.2071906. Online ahead of print.
Ref 3 METTL3 Promotes the Proliferation and Mobility of Gastric Cancer Cells. Open Med (Wars). 2019 Mar 2;14:25-31. doi: 10.1515/med-2019-0005. eCollection 2019.
Ref 4 METTL3 serves an oncogenic role in human ovarian cancer cells partially via the AKT signaling pathway. Oncol Lett. 2020 Apr;19(4):3197-3204. doi: 10.3892/ol.2020.11425. Epub 2020 Mar 3.
Ref 5 N(6)-Methyladenosine Associated Silencing of miR-193b Promotes Cervical Cancer Aggressiveness by Targeting CCND1. Front Oncol. 2021 Jun 10;11:666597. doi: 10.3389/fonc.2021.666597. eCollection 2021.
Ref 6 ZFP217 regulates adipogenesis by controlling mitotic clonal expansion in a METTL3-m(6)A dependent manner. RNA Biol. 2019 Dec;16(12):1785-1793. doi: 10.1080/15476286.2019.1658508. Epub 2019 Aug 27.
Ref 7 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 8 METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer. J Cell Mol Med. 2021 Jul;25(14):6602-6617. doi: 10.1111/jcmm.16664. Epub 2021 Jun 2.
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