m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00470)
Target Name DNA damage-inducible transcript 3 protein (DDIT3/CHOP)
Synonyms
DDIT-3; C/EBP zeta; C/EBP-homologous protein; CHOP; C/EBP-homologous protein 10; CHOP-10; CCAAT/enhancer-binding protein homologous protein; Growth arrest and DNA damage-inducible protein GADD153; CHOP; CHOP10; GADD153
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Gene Name DDIT3
Family bZIP family. {ECO:0000305}.
Function
Multifunctional transcription factor in endoplasmic reticulum (ER) stress response. Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress. Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP) function and as an activator of other genes (By similarity). Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression of C/EBP regulated genes (By similarity). Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L. Negatively regulates; expression of BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine synthetase (ASNS), CEBPA-dependent transcriptional activation of hepcidin (HAMP) and CEBPB-mediated expression of peroxisome proliferator-activated receptor gamma (PPARG) . Together with ATF4, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress (By similarity). Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity. Plays a regulatory role in the inflammatory response through the induction of caspase-11 (CASP4/CASP11) which induces the activation of caspase-1 (CASP1) and both these caspases increase the activation of pro-IL1B to mature IL1B which is involved in the inflammatory response (By similarity). Acts as a major regulator of postnatal neovascularization through regulation of endothelial nitric oxide synthase (NOS3)-related signaling (By similarity).
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Gene ID 9575
Uniprot ID
DDIT3_HUMAN
HGNC ID
HGNC:2726
Ensembl Gene ID
ENSG00000175197
KEGG ID
hsa:1649
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
DDIT3 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: shFTO NB4 cells
Control: shNS NB4 cells
 GSE103494
Regulation
logFC: 7.94E-01
p-value: 7.54E-04
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 Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Target Regulation Down regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Target Regulation Down regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Drug Fluorouracil Approved
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Target Regulation Down regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Drug Paclitaxel Approved
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line mouse embryonic stem cells Mus musculus
Treatment: METTL14-/- ESCs
Control: Wild type ESCs
 GSE145309
Regulation
logFC: -2.08E+00
p-value: 8.68E-26
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 [2]
Response Summary METTL14 promotes DNA damage-inducible transcript 3 protein (DDIT3/CHOP) mRNA decay through its 3' UTR N6-methyladenosine (m6A) to inhibit its downstream pro-apoptotic target gene expression, suppress ER proteotoxic liver disease. UPR induces METTL14 expression by competing against the HRD1-ER-associated degradation (ERAD) machinery to block METTL14 ubiquitination and degradation.
Target Regulation Down regulation
Responsed Disease Liver disease ICD-11: DB9Z
 Disease Info 
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Cell apoptosis
Ubiquitination degradation
In-vitro Model HEK293 Normal Homo sapiens CVCL_0045
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Fluorouracil Approved
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Experiment 3 Reporting the m6A-centered Disease Response [1]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Paclitaxel Approved
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Liver disease [ICD-11: DB9Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL14 promotes DNA damage-inducible transcript 3 protein (DDIT3/CHOP) mRNA decay through its 3' UTR N6-methyladenosine (m6A) to inhibit its downstream pro-apoptotic target gene expression, suppress ER proteotoxic liver disease. UPR induces METTL14 expression by competing against the HRD1-ER-associated degradation (ERAD) machinery to block METTL14 ubiquitination and degradation.
Responsed Disease Liver disease [ICD-11: DB9Z]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Cell apoptosis
Ubiquitination degradation
In-vitro Model HEK293 Normal Homo sapiens CVCL_0045
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Cisplatin [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Fluorouracil [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
Paclitaxel [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary Omeprazole pretreatment could enhance the inhibitory effect of 5-Fu, DDP and TAX on gastric cancer cells. FTO inhibition induced by omeprazole enhanced the activation of mTORC1 signal pathway that inhibited the prosurvival autophagy so as to improve the antitumor efficiency of chemotherapeutic drugs on GC cells. Meanwhile, transcript level of DNA damage-inducible transcript 3 protein (DDIT3), which is an apoptosis-related tumor suppressor gene downstream of mTORC1, was regulated by omeprazole-induced FTO silence through an m6A-dependent mechanism. m6A modification and its eraser FTO plays a role in the improvement of chemosensitivity mediated by proton pump inhibitor omeprazole.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
References
Ref 1 Omeprazole improves chemosensitivity of gastric cancer cells by m6A demethylase FTO-mediated activation of mTORC1 and DDIT3 up-regulation. Biosci Rep. 2021 Jan 29;41(1):BSR20200842. doi: 10.1042/BSR20200842.
Ref 2 HRD1-mediated METTL14 degradation regulates m(6)A mRNA modification to suppress ER proteotoxic liver disease. Mol Cell. 2021 Dec 16;81(24):5052-5065.e6. doi: 10.1016/j.molcel.2021.10.028. Epub 2021 Nov 29.