m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00225)
Target Name DNA damage-inducible transcript 4 protein (DDIT4)
Synonyms
HIF-1 responsive protein RTP801; Protein regulated in development and DNA damage response 1; REDD-1; REDD1; RTP801
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Gene Name DDIT4
Chromosomal Location 10q22.1
Family DDIT4 family
Function
Regulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage. Regulates p53/TP53-mediated apoptosis in response to DNA damage via its effect on mTORC1 activity. Its role in the response to hypoxia depends on the cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes, but not in hepatocytes (By similarity). Required for mTORC1-mediated defense against viral protein synthesis and virus replication (By similarity). Inhibits neuronal differentiation and neurite outgrowth mediated by NGF via its effect on mTORC1 activity. Required for normal neuron migration during embryonic brain development. Plays a role in neuronal cell death.
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Gene ID 54541
Uniprot ID
DDIT4_HUMAN
HGNC ID
HGNC:24944
Ensembl Gene ID
ENSG00000168209
KEGG ID
hsa:54541
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
DDIT4 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).
Browse Regulator
Browse Disease
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LX2 cell line Homo sapiens
Treatment: shMETTL3 LX2 cells
Control: shLuc LX2 cells
 GSE207909
Regulation
logFC: 1.24E+00
p-value: 1.11E-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 The contribution of METTL3-mediated m6A modification of DNA damage-inducible transcript 4 protein (DDIT4) mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and nuclear factor Kappa-B (NF-Kappa-B) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.
Target Regulation Down regulation
Responsed Disease Obesity ICD-11: 5B81
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
HIF-1 signaling pathway hsa04066
In-vivo Model The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary The contribution of METTL3-mediated m6A modification of DNA damage-inducible transcript 4 protein (DDIT4) mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and nuclear factor Kappa-B (NF-Kappa-B) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.
Target Regulation Down regulation
Responsed Disease Non-alcoholic fatty liver disease ICD-11: DB92
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
HIF-1 signaling pathway hsa04066
In-vivo Model The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors AHNAK and DNA damage-inducible transcript 4 protein (DDIT4) as m6A targets.
Target Regulation Up regulation
Responsed Disease Corneal injury ICD-11: NA06.4
 Disease Info 
Cell Process Cell proliferation
Cell migration
In-vitro Model CGC (Conjunctival goblet cells)
In-vivo Model Mettl3fl/wt mice were generated as previously described. Mettl3fl/wt mice were crossed with K14CreER mice to obtain K14creER/Mettl3fl/fl (cKO) mice. Mettl3 cKO and control mice were injected with tamoxifen and then were subjected to corneal alkali burn treatment. The right eye was the experimental eye, and the left eye was the control eye. The mice were sacrificed at 24 hours, 7 days, 14 days, 35 days, and 56 days after injury. Six mice were taken from each period. Both eyes were removed, frozen in OCT (n = 4), fixed in 4% paraformaldehyde, and embedded in conventional paraffin (n = 2).
Obesity [ICD-11: 5B81]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary The contribution of METTL3-mediated m6A modification of DNA damage-inducible transcript 4 protein (DDIT4) mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and nuclear factor Kappa-B (NF-Kappa-B) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.
Responsed Disease Obesity [ICD-11: 5B81]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
HIF-1 signaling pathway hsa04066
In-vivo Model The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Non-alcoholic fatty liver disease [ICD-11: DB92]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary The contribution of METTL3-mediated m6A modification of DNA damage-inducible transcript 4 protein (DDIT4) mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and nuclear factor Kappa-B (NF-Kappa-B) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.
Responsed Disease Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
HIF-1 signaling pathway hsa04066
In-vivo Model The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Corneal injury [ICD-11: NA06]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors AHNAK and DNA damage-inducible transcript 4 protein (DDIT4) as m6A targets.
Responsed Disease Corneal injury [ICD-11: NA06.4]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell proliferation
Cell migration
In-vitro Model CGC (Conjunctival goblet cells)
In-vivo Model Mettl3fl/wt mice were generated as previously described. Mettl3fl/wt mice were crossed with K14CreER mice to obtain K14creER/Mettl3fl/fl (cKO) mice. Mettl3 cKO and control mice were injected with tamoxifen and then were subjected to corneal alkali burn treatment. The right eye was the experimental eye, and the left eye was the control eye. The mice were sacrificed at 24 hours, 7 days, 14 days, 35 days, and 56 days after injury. Six mice were taken from each period. Both eyes were removed, frozen in OCT (n = 4), fixed in 4% paraformaldehyde, and embedded in conventional paraffin (n = 2).
References
Ref 1 m(6)A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Rep. 2021 Nov 9;37(6):109968. doi: 10.1016/j.celrep.2021.109968.
Ref 2 METTL3-Mediated m(6)A RNA Modification Regulates Corneal Injury Repair. Stem Cells Int. 2021 Oct 22;2021:5512153. doi: 10.1155/2021/5512153. eCollection 2021.