m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00356)
Target Name Cellular tumor antigen p53 (TP53/p53)
Synonyms
Antigen NY-CO-13; Phosphoprotein p53; Tumor suppressor p53; P53
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Gene Name TP53
Chromosomal Location 17p13.1
Family p53 family
Function
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2. However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2.
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Gene ID 7157
Uniprot ID
P53_HUMAN
HGNC ID
HGNC:11998
Ensembl Gene ID
ENSG00000141510
KEGG ID
hsa:7157
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
TP53 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]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line HeLa cell line Homo sapiens
Treatment: METTL3 knockdown HeLa cells
Control: HeLa cells
 GSE70061
Regulation
logFC: 1.12E+00
p-value: 1.48E-02
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between TP53 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 2.05E+00 GSE60213
In total 6 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Silencing the m(6)A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the Cellular tumor antigen p53 (TP53/p53) (also known as TP53) signalling pathway and apoptosis. Modulation of p53 signalling through splicing is relevant to induction of apoptosis by silencing of METTL3.
Target Regulation Down regulation
Pathway Response Apoptosis hsa04210
p53 signaling pathway hsa04115
Cell Process Gene expression
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 significantly decreased m6A level, restoring Cellular tumor antigen p53 (TP53/p53) activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.
Target Regulation Up regulation
Responsed Disease Solid tumour/cancer ICD-11: 2A00-2F9Z
 Disease Info 
Responsed Drug Arsenite Phase 2
 Drug Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/Cellular tumor antigen p53 (TP53/p53) signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2.
Target Regulation Down regulation
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
Cell cycle hsa04110
Apoptosis hsa04210
Cell Process Cell apoptosis
Cells in G3/M phase decreased
In-vitro Model THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
MOLT-4 Adult T acute lymphoblastic leukemia Homo sapiens CVCL_0013
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
HEL Erythroleukemia Homo sapiens CVCL_0001
CCRF-CEM C7 T acute lymphoblastic leukemia Homo sapiens CVCL_6825
HEK293T Normal Homo sapiens CVCL_0063
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary The produced p53 R273H mutant protein resulted in acquired multidrug resistance in colon cancer cells. Either silencing METTL3 expression by using small interfering RNA (siRNA) or inhibiting RNA methylation with neplanocin A suppressed m6A formation in Cellular tumor antigen p53 (TP53/p53) pre-mRNA, and substantially increased the level of phosphorylated p53 protein (Ser15) and its function in cells heterozygously carrying the R273H mutation, thereby re-sensitizing these cells to anticancer drugs.
Target Regulation Up regulation
Responsed Disease Colon cancer ICD-11: 2B90
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
Cell Process Protein signaling
In-vitro Model SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
WiDr Colon adenocarcinoma Homo sapiens CVCL_2760
Experiment 5 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Responsed Drug Apatinib Approved
 Drug Info 
Pathway Response p53 signaling pathway hsa04115
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model QGY-7701 Human papillomavirus-related endocervical adenocarcinoma Homo sapiens CVCL_6859
HHL-5 Normal Homo sapiens CVCL_S956
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Experiment 6 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Responsed Drug RG7112 Phase 1
 Drug Info 
Pathway Response p53 signaling pathway hsa04115
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model QGY-7701 Human papillomavirus-related endocervical adenocarcinoma Homo sapiens CVCL_6859
HHL-5 Normal Homo sapiens CVCL_S956
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced acute kidney injury Acute kidney injury.
Target Regulation Down regulation
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced Acute kidney injury.
Target Regulation Down regulation
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Responsed Drug Meclofenamic acid Approved
 Drug Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/Cellular tumor antigen p53 (TP53/p53) signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2.
Target Regulation Down regulation
Responsed Disease Acute myeloid leukaemia ICD-11: 2A60
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
Cell cycle hsa04110
Apoptosis hsa04210
Cell Process Cell apoptosis
Cells in G6/M phase decreased
In-vitro Model THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
MOLT-4 Adult T acute lymphoblastic leukemia Homo sapiens CVCL_0013
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
HEL Erythroleukemia Homo sapiens CVCL_0001
CCRF-CEM C7 T acute lymphoblastic leukemia Homo sapiens CVCL_6825
HEK293T Normal Homo sapiens CVCL_0063
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 [7]
Response Summary Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [7]
Response Summary Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [8]
Response Summary Knockdown of Cellular tumor antigen p53 (TP53/p53) or inhibition of p53's transcriptional activity by addition of its specific inhibitor PFT-Alpha decreased expression of ALKBH5 and Cancer stem cells' malignancies, the pivotal role of ALKBH5 in Cancer stem cells derived from nonsmall-cell lung cancer and highlight the regulatory function of the p53/ALKBH5 axis in modulating CSC progression. p53 transcriptionally regulates PRRX1, which is consistent with our previous report.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model Cells at 1 × 106 were subcutaneously injected into the mice similarly to nude mice. Twenty-eight days later, grafted tumors were collected and morphologically analyzed.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [9]
Response Summary ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo. Alkbh5-deficient male mice have increased m(6)A in mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. Identified in mouse testes 1,551 differentially expressed genes that cover broad functional categories and include spermatogenesis-related mRNAs involved in the Cellular tumor antigen p53 (TP53/p53) functional interaction network.
Responsed Disease Female reproductive system disorders ICD-11: SC4Y
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
In-vivo Model Neo-resistant recombinant ESCs were analyzed for correct 3' and 5' targeting through hybridization by standard protocols, and we identified seven correctly targeted clones. Following ESC cell injection, several high-percentage chimera males were born. These were bred with Cre-expressing mice, and Cre-mediated excision of Alkbh5 exon 1 was tested in 26 agouti F1 pups. Two animals tested positive for the excised allele. These two mice, heterozygous for the constitutive allele (Alkbh5+/-), were analyzed by Southern blot analysis and used for further breeding to generate Alkbh5-/- mice.
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 [2]
Response Summary METTL3 significantly decreased m6A level, restoring Cellular tumor antigen p53 (TP53/p53) activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.
Target Regulation Down regulation
Responsed Disease Solid tumour/cancer ICD-11: 2A00-2F9Z
 Disease Info 
Responsed Drug Arsenite Phase 2
 Drug Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 significantly decreased m6A level, restoring Cellular tumor antigen p53 (TP53/p53) activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.
Responsed Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Arsenite Phase 2
 Drug Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 significantly decreased m6A level, restoring Cellular tumor antigen p53 (TP53/p53) activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.
Responsed Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Arsenite Phase 2
 Drug Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
Acute myeloid leukaemia [ICD-11: 2A60]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/Cellular tumor antigen p53 (TP53/p53) signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2.
Responsed Disease Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response p53 signaling pathway hsa04115
Cell cycle hsa04110
Apoptosis hsa04210
Cell Process Cell apoptosis
Cells in G6/M phase decreased
In-vitro Model THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
MOLT-4 Adult T acute lymphoblastic leukemia Homo sapiens CVCL_0013
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
HEL Erythroleukemia Homo sapiens CVCL_0001
CCRF-CEM C7 T acute lymphoblastic leukemia Homo sapiens CVCL_6825
HEK293T Normal Homo sapiens CVCL_0063
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/Cellular tumor antigen p53 (TP53/p53) signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2.
Responsed Disease Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response p53 signaling pathway hsa04115
Cell cycle hsa04110
Apoptosis hsa04210
Cell Process Cell apoptosis
Cells in G3/M phase decreased
In-vitro Model THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
MV4-11 Childhood acute monocytic leukemia Homo sapiens CVCL_0064
MOLT-4 Adult T acute lymphoblastic leukemia Homo sapiens CVCL_0013
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
HEL Erythroleukemia Homo sapiens CVCL_0001
CCRF-CEM C7 T acute lymphoblastic leukemia Homo sapiens CVCL_6825
HEK293T Normal Homo sapiens CVCL_0063
Colon cancer [ICD-11: 2B90]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary Colon cancer cell lines, either WiDr homozygous for missense-mutated Cellular tumor antigen p53 (TP53/p53) (R273H) or SW48/TP53-Dox bearing heterozygous TP53 mutant (R273H), display drug resistance with increased ceramide glycosylation. Increased Gb3-cSrc complex in GEMs of membranes in response to anticancer drug induced cell stress promotes expression of p53 mutant proteins and accordant cancer drug resistance. Genz-161 effectively inhibited GCS activity, and substantially suppressed the elevated Gb3 levels seen in GEMs of p53-mutant cells exposed to doxorubicin.
Responsed Disease Colon cancer [ICD-11: 2B90]
Pathway Response Apoptosis hsa04210
Wnt signaling pathway hsa04310
Cell Process Cellular stress
Cell apoptosis
In-vitro Model SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
In-vivo Model Cell suspension of SW48 or SW48/TP53 (5-7 passages, 1 × 106 cells in 20 uL/mouse) was subcutaneously injected into the left flank of the mice.
Experiment 2 Reporting the m6A-centered Disease Response [4]
Response Summary The produced p53 R273H mutant protein resulted in acquired multidrug resistance in colon cancer cells. Either silencing METTL3 expression by using small interfering RNA (siRNA) or inhibiting RNA methylation with neplanocin A suppressed m6A formation in Cellular tumor antigen p53 (TP53/p53) pre-mRNA, and substantially increased the level of phosphorylated p53 protein (Ser15) and its function in cells heterozygously carrying the R273H mutation, thereby re-sensitizing these cells to anticancer drugs.
Responsed Disease Colon cancer [ICD-11: 2B90]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response p53 signaling pathway hsa04115
Cell Process Protein signaling
In-vitro Model SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
WiDr Colon adenocarcinoma Homo sapiens CVCL_2760
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 4 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [7]
Response Summary Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 16 (METTL16) WRITER
 Regulator Info 
Experiment 2 Reporting the m6A-centered Disease Response [5]
Response Summary Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Apatinib Approved
 Drug Info 
Pathway Response p53 signaling pathway hsa04115
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model QGY-7701 Human papillomavirus-related endocervical adenocarcinoma Homo sapiens CVCL_6859
HHL-5 Normal Homo sapiens CVCL_S956
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Experiment 3 Reporting the m6A-centered Disease Response [5]
Response Summary Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug RG7112 Phase 1
 Drug Info 
Pathway Response p53 signaling pathway hsa04115
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model QGY-7701 Human papillomavirus-related endocervical adenocarcinoma Homo sapiens CVCL_6859
HHL-5 Normal Homo sapiens CVCL_S956
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Experiment 4 Reporting the m6A-centered Disease Response [7]
Response Summary Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [8]
Response Summary Knockdown of Cellular tumor antigen p53 (TP53/p53) or inhibition of p53's transcriptional activity by addition of its specific inhibitor PFT-Alpha decreased expression of ALKBH5 and Cancer stem cells' malignancies, the pivotal role of ALKBH5 in Cancer stem cells derived from nonsmall-cell lung cancer and highlight the regulatory function of the p53/ALKBH5 axis in modulating CSC progression. p53 transcriptionally regulates PRRX1, which is consistent with our previous report.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response p53 signaling pathway hsa04115
In-vitro Model PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model Cells at 1 × 106 were subcutaneously injected into the mice similarly to nude mice. Twenty-eight days later, grafted tumors were collected and morphologically analyzed.
Acute kidney failure [ICD-11: GB60]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [6]
Response Summary Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced acute kidney injury Acute kidney injury.
Responsed Disease Acute kidney failure [ICD-11: GB60]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Experiment 2 Reporting the m6A-centered Disease Response [6]
Response Summary Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced Acute kidney injury.
Responsed Disease Acute kidney failure [ICD-11: GB60]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Meclofenamic acid Approved
 Drug Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Cerebral development anomalies [ICD-11: LA05]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary Post-transcriptional regulation by the exosome complex is required for cell survival and forebrain development via repression of Cellular tumor antigen p53 (TP53/p53) signaling. N6-methyladenosine (m6A) methylation-mediated degradation of RNA is essential for brain development,m6A methylation impacts not only RNA stability, but also other RNA metabolism processes. Exosc10 in suppressing the P53 pathway, in which the rapid turnover of the apoptosis effectors Aen and Bbc3 mRNAs is essential for cell survival and normal cortical histogenesis.
Responsed Disease Cerebral development anomalies [ICD-11: LA05]
Pathway Response p53 signaling pathway hsa04115
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vivo Model Exosc10cKO_Emx1-Cre mouse embryos were subjected to the p53-inhibitor Pifithrin-Alpha (PFT-Alpha) by intraperitoneal injection of 2.2 mg/kg PFT-Alpha (Selleckchem) into the pregnant mother at between E9.5 and E12.5 or between E9.5 and E15.5. Embryonic brains were isolated at E13.5 or E18.5 and immunohistochemistry was performed.
Female reproductive system disorders [ICD-11: SC4Y]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [9]
Response Summary ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo. Alkbh5-deficient male mice have increased m(6)A in mRNA and are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. Identified in mouse testes 1,551 differentially expressed genes that cover broad functional categories and include spermatogenesis-related mRNAs involved in the Cellular tumor antigen p53 (TP53/p53) functional interaction network.
Responsed Disease Female reproductive system disorders [ICD-11: SC4Y]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
In-vivo Model Neo-resistant recombinant ESCs were analyzed for correct 3' and 5' targeting through hybridization by standard protocols, and we identified seven correctly targeted clones. Following ESC cell injection, several high-percentage chimera males were born. These were bred with Cre-expressing mice, and Cre-mediated excision of Alkbh5 exon 1 was tested in 26 agouti F1 pups. Two animals tested positive for the excised allele. These two mice, heterozygous for the constitutive allele (Alkbh5+/-), were analyzed by Southern blot analysis and used for further breeding to generate Alkbh5-/- mice.
Apatinib [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [5]
Response Summary Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model QGY-7701 Human papillomavirus-related endocervical adenocarcinoma Homo sapiens CVCL_6859
HHL-5 Normal Homo sapiens CVCL_S956
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Cisplatin [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [6]
Response Summary Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced acute kidney injury Acute kidney injury.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Meclofenamic acid [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [6]
Response Summary Meclofenamic acid increased Cellular tumor antigen p53 (TP53/p53) mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in cisplatin-induced Acute kidney injury.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days.
Arsenite [Phase 2]
 Drug Info 
In total 2 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [2]
Response Summary METTL3 significantly decreased m6A level, restoring Cellular tumor antigen p53 (TP53/p53) activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Solid tumour/cancer ICD-11: 2A00-2F9Z
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
Experiment 2 Reporting the m6A-centered Drug Response [2]
Response Summary METTL3 significantly decreased m6A level, restoring Cellular tumor antigen p53 (TP53/p53) activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Solid tumour/cancer ICD-11: 2A00-2F9Z
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
In-vitro Model HaCaT Normal Homo sapiens CVCL_0038
RG7112 [ Phase 1]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [5]
Response Summary Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model QGY-7701 Human papillomavirus-related endocervical adenocarcinoma Homo sapiens CVCL_6859
HHL-5 Normal Homo sapiens CVCL_S956
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 107 HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
References
Ref 1 Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012 Apr 29;485(7397):201-6. doi: 10.1038/nature11112.
Ref 2 N(6)-methyladenosine mediates arsenite-induced human keratinocyte transformation by suppressing p53 activation. Environ Pollut. 2020 Apr;259:113908. doi: 10.1016/j.envpol.2019.113908. Epub 2020 Jan 7.
Ref 3 The m(6)A RNA methyltransferase METTL3/METTL14 promotes leukemogenesis through the mdm2/p53 pathway in acute myeloid leukemia. J Cancer. 2022 Jan 4;13(3):1019-1030. doi: 10.7150/jca.60381. eCollection 2022.
Ref 4 An N(6)-methyladenosine at the transited codon 273 of p53 pre-mRNA promotes the expression of R273H mutant protein and drug resistance of cancer cells. Biochem Pharmacol. 2019 Feb;160:134-145. doi: 10.1016/j.bcp.2018.12.014. Epub 2018 Dec 19.
Ref 5 p53 m(6)A modulation sensitizes hepatocellular carcinoma to apatinib through apoptosis. Apoptosis. 2022 Jun;27(5-6):426-440. doi: 10.1007/s10495-022-01728-x. Epub 2022 May 3.
Ref 6 Meclofenamic acid promotes cisplatin-induced acute kidney injury by inhibiting fat mass and obesity-associated protein-mediated m(6)A abrogation in RNA. J Biol Chem. 2019 Nov 8;294(45):16908-16917. doi: 10.1074/jbc.RA119.011009. Epub 2019 Oct 2.
Ref 7 Gene Signatures and Prognostic Values of m6A Regulators in Hepatocellular Carcinoma. Front Genet. 2020 Oct 2;11:540186. doi: 10.3389/fgene.2020.540186. eCollection 2020.
Ref 8 RNA Demethylase ALKBH5 Prevents Lung Cancer Progression by Regulating EMT and Stemness via Regulating p53. Front Oncol. 2022 Apr 22;12:858694. doi: 10.3389/fonc.2022.858694. eCollection 2022.
Ref 9 ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013 Jan 10;49(1):18-29. doi: 10.1016/j.molcel.2012.10.015. Epub 2012 Nov 21.