m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00700)
Target Name Proto-oncogene c-Rel (c-Rel)
Gene Name c-Rel
Chromosomal Location 2p16.1
Function
Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed 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 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. 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 NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.
    Click to Show/Hide
Gene ID 5966
Uniprot ID
REL_HUMAN
HGNC ID
HGNC:9954
Ensembl Gene ID
ENSG00000162924
KEGG ID
hsa:5966
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
c-Rel 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 Pancreatic islets Mus musculus
Treatment: Mettl3 knockout mice
Control: Mettl3 flox/flox mice
 GSE155612
Regulation
logFC: 1.39E+00
p-value: 2.50E-05
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between c-Rel and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 2.02E+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 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through Proto-oncogene c-Rel (c-Rel) and 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 Mouse-cerebellum granule cell Mus musculus
Treatment: YTHDF2 knockdown mouse-cerebellum granule cell
Control: Wild type mouse-cerebellum granule cell
 GSE153688
Regulation
logFC: 9.51E-01
p-value: 8.19E-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 [1]
Response Summary METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through Proto-oncogene c-Rel (c-Rel) and 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).
Thyroid Cancer [ICD-11: 2D10]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through Proto-oncogene c-Rel (c-Rel) and 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 [1]
Response Summary METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through Proto-oncogene c-Rel (c-Rel) and 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).
References
Ref 1 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.