m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00425)
Target Name Transcription factor p65 (RELA)
Synonyms
Nuclear factor NF-kappa-B p65 subunit; Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3; NFKB3
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Gene Name RELA
Chromosomal Location 11q13.1
Function
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells . The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infectio.
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Gene ID 5970
Uniprot ID
TF65_HUMAN
HGNC ID
HGNC:9955
Ensembl Gene ID
ENSG00000173039
KEGG ID
hsa:5970
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
RELA 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 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line BMDM Mus musculus
Treatment: METTL14 knockout mice BMDM
Control: Wild type mice BMDM
 GSE153512
Regulation
logFC: 7.00E-01
p-value: 8.41E-10
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 [1]
Response Summary Knocking down METTL14 could inhibit the development of atherosclerosis in high-fat diet-treated APOE mice. After transfection with si-METTL14, the bcl-2 expression level and the viability of ox-LDL-incubated cells increased, whereas the apoptosis rate and the expressions of Bax and cleaved caspase-3 decreased. However, the effect of METTL14 knockdown was reversed by Transcription factor p65 (RELA) overexpression.
Target Regulation Up regulation
Responsed Disease Atherosclerosis ICD-11: BD40.Z
 Disease Info 
Cell Process Cell apoptosis
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
EA.hy 926 Normal Homo sapiens CVCL_3901
In-vivo Model The mice were randomly divided into control, Ad-sh-NC, and Ad-sh-METTL14 groups (10 mice per group). The mice in the control group were fed a normal diet, while the Ad-sh-NC and Ad-sh-METTL14 groups were fed a high-fat diet (20% fat and 0.25% cholesterol). Furthermore, 300 uL of constructed sh-NC or sh-METTL14 adenovirus was injected every 3 weeks into the caudal veins of mice from the Ad-sh-NC or Ad-sh-METTL14 groups, respectively. The constructed vectors were obtained from HanBio Technology Co., Ltd. (Shanghai, China). All mice were sacrificed after 24 weeks and the aortas were separated for further experiments.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line Caco-2 cell line Homo sapiens
Treatment: shMETTL3 Caco-2 cells
Control: shNTC Caco-2 cells
 GSE167075
Regulation
logFC: 6.33E-01
p-value: 3.93E-11
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 [2]
Response Summary AF4/FMR2 family member 4 (AFF4), two key regulators of NF-Kappa-B pathway (IKBKB and Transcription factor p65 (RELA)) and MYC were further identified as direct targets of METTL3-mediated m6A modification.overexpression of METTL3 significantly promoted Bladder cancer cell growth and invasion.
Target Regulation Up regulation
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Cell Process Glucose metabolism
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through c-Rel and Transcription factor p65 (RELA) inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.
Target Regulation Down regulation
Responsed Disease Papillary thyroid cancer ICD-11: 2D10.1
 Disease Info 
Pathway Response NF-kappa B signaling pathway hsa04064
In-vitro Model TPC-1 Thyroid gland papillary carcinoma Homo sapiens CVCL_6298
Nthy-ori 3-1 Normal Homo sapiens CVCL_2659
KTC-1 Thyroid carcinoma Homo sapiens CVCL_6300
B-CPAP Thyroid gland carcinoma Homo sapiens CVCL_0153
In-vivo Model For xenograft models, 5 × 106 BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 106 cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 106 cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
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: 6.31E-01
p-value: 1.53E-07
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 [3]
Response Summary METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through c-Rel and Transcription factor p65 (RELA) inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.
Target Regulation Down regulation
Responsed Disease Papillary thyroid cancer ICD-11: 2D10.1
 Disease Info 
Pathway Response NF-kappa B signaling pathway hsa04064
In-vitro Model TPC-1 Thyroid gland papillary carcinoma Homo sapiens CVCL_6298
Nthy-ori 3-1 Normal Homo sapiens CVCL_2659
KTC-1 Thyroid carcinoma Homo sapiens CVCL_6300
B-CPAP Thyroid gland carcinoma Homo sapiens CVCL_0153
In-vivo Model For xenograft models, 5 × 106 BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 106 cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 106 cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
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 [4]
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 Transcription factor p65 (RELA), IL-1-beta and 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
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 3 (YTHDF3) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [4]
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 Transcription factor p65 (RELA), IL-1-beta and 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.
Bladder cancer [ICD-11: 2C94]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary AF4/FMR2 family member 4 (AFF4), two key regulators of NF-Kappa-B pathway (IKBKB and Transcription factor p65 (RELA)) and MYC were further identified as direct targets of METTL3-mediated m6A modification.overexpression of METTL3 significantly promoted Bladder cancer cell growth and invasion.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Glucose metabolism
Thyroid Cancer [ICD-11: 2D10]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through c-Rel and Transcription factor p65 (RELA) inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.
Responsed Disease Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response NF-kappa B signaling pathway hsa04064
In-vitro Model TPC-1 Thyroid gland papillary carcinoma Homo sapiens CVCL_6298
Nthy-ori 3-1 Normal Homo sapiens CVCL_2659
KTC-1 Thyroid carcinoma Homo sapiens CVCL_6300
B-CPAP Thyroid gland carcinoma Homo sapiens CVCL_0153
In-vivo Model For xenograft models, 5 × 106 BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 106 cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 106 cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through c-Rel and Transcription factor p65 (RELA) inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.
Responsed Disease Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response NF-kappa B signaling pathway hsa04064
In-vitro Model TPC-1 Thyroid gland papillary carcinoma Homo sapiens CVCL_6298
Nthy-ori 3-1 Normal Homo sapiens CVCL_2659
KTC-1 Thyroid carcinoma Homo sapiens CVCL_6300
B-CPAP Thyroid gland carcinoma Homo sapiens CVCL_0153
In-vivo Model For xenograft models, 5 × 106 BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 106 cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 106 cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
Atherosclerosis [ICD-11: BD40]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Knocking down METTL14 could inhibit the development of atherosclerosis in high-fat diet-treated APOE mice. After transfection with si-METTL14, the bcl-2 expression level and the viability of ox-LDL-incubated cells increased, whereas the apoptosis rate and the expressions of Bax and cleaved caspase-3 decreased. However, the effect of METTL14 knockdown was reversed by Transcription factor p65 (RELA) overexpression.
Responsed Disease Atherosclerosis [ICD-11: BD40.Z]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell apoptosis
In-vitro Model HUVEC-C Normal Homo sapiens CVCL_2959
EA.hy 926 Normal Homo sapiens CVCL_3901
In-vivo Model The mice were randomly divided into control, Ad-sh-NC, and Ad-sh-METTL14 groups (10 mice per group). The mice in the control group were fed a normal diet, while the Ad-sh-NC and Ad-sh-METTL14 groups were fed a high-fat diet (20% fat and 0.25% cholesterol). Furthermore, 300 uL of constructed sh-NC or sh-METTL14 adenovirus was injected every 3 weeks into the caudal veins of mice from the Ad-sh-NC or Ad-sh-METTL14 groups, respectively. The constructed vectors were obtained from HanBio Technology Co., Ltd. (Shanghai, China). All mice were sacrificed after 24 weeks and the aortas were separated for further experiments.
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 [4]
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 Transcription factor p65 (RELA), IL-1-beta and 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
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 [4]
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 Transcription factor p65 (RELA), IL-1-beta and 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.
References
Ref 1 Methyltransferase-like 14 silencing relieves the development of atherosclerosis via m(6)A modification of p65 mRNA. Bioengineered. 2022 May;13(5):11832-11843. doi: 10.1080/21655979.2022.2031409.
Ref 2 The m(6)A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-KappaB/MYC signaling network. Oncogene. 2019 May;38(19):3667-3680. doi: 10.1038/s41388-019-0683-z. Epub 2019 Jan 18.
Ref 3 METTL3 restrains papillary thyroid cancer progression via m(6)A/c-Rel/IL-8-mediated neutrophil infiltration. Mol Ther. 2021 May 5;29(5):1821-1837. doi: 10.1016/j.ymthe.2021.01.019. Epub 2021 Jan 21.
Ref 4 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.