m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00432)
Target Name Tumor necrosis factor (TNF/TNF-alpha)
Synonyms
Cachectin; TNF-alpha; Tumor necrosis factor ligand superfamily member 2; TNF-a; N-terminal fragment; NTF; ICD1; ICD2; TNFA; TNFSF2
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Gene Name TNF
Chromosomal Location 6p21.33
Family tumor necrosis factor family
Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective. Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line. Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6; The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
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Gene ID 7124
Uniprot ID
TNFA_HUMAN
HGNC ID
HGNC:11892
Ensembl Gene ID
ENSG00000204490; ENSG00000206439; ENSG00000228321; ENSG00000228849; ENSG00000230108; ENSG00000223952; ENSG00000232810
KEGG ID
hsa:7124
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
TNF 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 Raw 264.7 cell line Mus musculus
Treatment: METTL3 knockout Raw 264.7 cells
Control: Wild type Raw 264.7 cells
 GSE162248
Regulation
logFC: -8.06E-01
p-value: 1.88E-29
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between TNF and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 4.17E+00 GSE60213
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Target Regulation Up regulation
Responsed Disease B-cell lymphomas ICD-11: 2A86
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line CT26 cell line Mus musculus
Treatment: METTL14 knockout CT26 cells
Control: CT26 cells
 GSE142589
Regulation
logFC: 1.47E+00
p-value: 1.57E-04
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 could aggravated high glucose-induced glomerular endothelial cell injury and diabetic nephropathy through m6A modification of alpha-klotho. METTL14 silence decreased the levels of ROS, Tumor necrosis factor (TNF/TNF-alpha) and IL-6 and cell apoptosis.
Target Regulation Up regulation
Responsed Disease Chronic kidney disease ICD-11: GB61.Z
 Disease Info 
Pathway Response NF-kappa B signaling pathway hsa04064
AGE-RAGE signaling pathway in diabetic complications hsa04933
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HRGECs cell line (Human glomerular microvascular endothelial cells)
In-vivo Model After adaptive feeding for 1 week, db/db mice were randomly divided into five groups (n = 6): db/db group, db/db + rAAV group, db/db + rAAV-METTL14 group, db/db + rAAV-klotho group, and db/db + rAAV-METTL14 + rAAV-klotho group. Except db/db group, the other four groups were injected with recombinant adeno-associated virus (rAAV) control, rAAV mediated delivery of METTL14 (rAAV-METTL14), or/and rAAV mediated delivery of klotho (rAAV-klotho) respectively via tail vein. Six db/m mice were chosen as the normal control.
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and Tumor necrosis factor (TNF/TNF-alpha) secretion.
Target Regulation Up regulation
Responsed Disease Gangrene or necrosis of lung ICD-11: CA43
 Disease Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Target Regulation Up regulation
Responsed Disease B-cell lymphomas ICD-11: 2A86
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
YTH domain-containing family protein 3 (YTHDF3) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and Tumor necrosis factor (TNF/TNF-alpha) secretion.
Target Regulation Up regulation
Responsed Disease Gangrene or necrosis of lung ICD-11: CA43
 Disease Info 
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
B-cell lymphomas [ICD-11: 2A86]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Responsed Disease B-cell lymphomas [ICD-11: 2A86]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Responsed Disease B-cell lymphomas [ICD-11: 2A86]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Gangrene or necrosis of lung [ICD-11: CA43]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and Tumor necrosis factor (TNF/TNF-alpha) secretion.
Responsed Disease Gangrene or necrosis of lung [ICD-11: CA43]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of lung ischemia-reperfusion injury. YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-Kappa-B pathways in BEAS-2B cells, and inhibited p-p65, IL-1-beta and Tumor necrosis factor (TNF/TNF-alpha) secretion.
Responsed Disease Gangrene or necrosis of lung [ICD-11: CA43]
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
PI3K-Akt signaling pathway hsa04151
Apoptosis hsa04210
Cell Process Biological regulation
Cell apoptosis
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
In-vivo Model After being anesthetized with urethane (i.p.), SD rats were endotracheally intubated and ventilated using an animal ventilator under the conditions: respiratory rate of 70 breaths/min, tidal volume of 20 ml/kg, and inspiratory/expiratory ratio of 1:1.
Dentofacial anomalies [ICD-11: DA0E]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Responsed Disease Temporomandibular joint disorders [ICD-11: DA0E.8]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.
Responsed Disease Temporomandibular joint disorders [ICD-11: DA0E.8]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Apoptosis hsa04210
Cell Process Cell proliferation and metastasis
Cell apoptosis
In-vitro Model ATDC-5 Mouse teratocarcinoma Mus musculus CVCL_3894
In-vivo Model For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Chronic kidney disease [ICD-11: GB61]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL14 could aggravated high glucose-induced glomerular endothelial cell injury and diabetic nephropathy through m6A modification of alpha-klotho. METTL14 silence decreased the levels of ROS, Tumor necrosis factor (TNF/TNF-alpha) and IL-6 and cell apoptosis.
Responsed Disease Chronic kidney disease [ICD-11: GB61.Z]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response NF-kappa B signaling pathway hsa04064
AGE-RAGE signaling pathway in diabetic complications hsa04933
Apoptosis hsa04210
Cell Process Cell apoptosis
In-vitro Model HRGECs cell line (Human glomerular microvascular endothelial cells)
In-vivo Model After adaptive feeding for 1 week, db/db mice were randomly divided into five groups (n = 6): db/db group, db/db + rAAV group, db/db + rAAV-METTL14 group, db/db + rAAV-klotho group, and db/db + rAAV-METTL14 + rAAV-klotho group. Except db/db group, the other four groups were injected with recombinant adeno-associated virus (rAAV) control, rAAV mediated delivery of METTL14 (rAAV-METTL14), or/and rAAV mediated delivery of klotho (rAAV-klotho) respectively via tail vein. Six db/m mice were chosen as the normal control.
References
Ref 1 Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through mediating Bcl2 stability via Ythdf1-mediated m(6)A modification. Bone. 2022 Jan;154:116182. doi: 10.1016/j.bone.2021.116182. Epub 2021 Sep 13.
Ref 2 METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of Alpha-klotho. Mol Med. 2021 Sep 9;27(1):106. doi: 10.1186/s10020-021-00365-5.
Ref 3 N6-methyladenosine reader YTH N6-methyladenosine RNA binding protein 3 or insulin like growth factor 2 mRNA binding protein 2 knockdown protects human bronchial epithelial cells from hypoxia/reoxygenation injury by inactivating p38 MAPK, AKT, ERK1/2, and NF-KappaB pathways. Bioengineered. 2022 May;13(5):11973-11986. doi: 10.1080/21655979.2021.1999550.