General Information of the Disease (ID: M6ADIS0125)
Name
Inflammatory response
ICD
ICD-11: MG46
Full List of Target Gene(s) of This m6A-centered Disease Response
E3 ubiquitin-protein ligase SMURF1 (SMURF1)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Smad7 and E3 ubiquitin-protein ligase SMURF1 (SMURF1) mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.
Responsed Disease Inflammatory response [ICD-11: MG46]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Pathway Response MAPK signaling pathway hsa04010
Cell Process RNA stability
In-vitro Model MC3T3-E1 Normal Mus musculus CVCL_0409
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Smad7 and E3 ubiquitin-protein ligase SMURF1 (SMURF1) mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.
Responsed Disease Inflammatory response [ICD-11: MG46]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Pathway Response MAPK signaling pathway hsa04010
Cell Process RNA stability
In-vitro Model MC3T3-E1 Normal Mus musculus CVCL_0409
Forkhead box protein O3 (FOXO3)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary YTHDF3 as a negative regulator of antiviral immunity through the translational promotion of Forkhead box protein O3 (FOXO3) mRNA under homeostatic conditions, adding insight into the networks of RNA-binding protein-RNA interactions in homeostatically maintaining host antiviral immune function and preventing inflammatory response.
Responsed Disease Inflammatory response [ICD-11: MG46]
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
In-vivo Model YTHDF3-/- mice were generated using the CRISPR-Cas9 system.
HPK/GCK-like kinase HGK (MAP4K4)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary YTHDF2 knockdown increases mRNA expression levels of MAP2K4 and HPK/GCK-like kinase HGK (MAP4K4) via stabilizing the mRNA transcripts, which activate MAPK and NF-Kappa-B signaling pathways, which promote the expression of proinflammatory cytokines and aggravate the inflammatory response in LPS-stimulated RAW 264.7 cells.
Responsed Disease Inflammatory response [ICD-11: MG46]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Pathway Response MAPK signaling pathway hsa04010
In-vitro Model RAW 264.7 Mouse leukemia Mus musculus CVCL_0493
Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [5]
Response Summary Lnc-Dpf3 directly bound to Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A) and suppressed HIF-1-alpha-dependent transcription of the glycolytic gene Ldha, thus inhibiting DC glycolytic metabolism and migratory capacity. CCR7-inducible lnc-Dpf3 in coupling epigenetic and metabolic pathways to feedback-control DC migration and inflammatory responses.
Responsed Disease Inflammatory response [ICD-11: MG46]
Pathway Response HIF-1 signaling pathway hsa04066
Cell Process Glycolysis
Immune responses
Inflammatory injuries
In-vitro Model CD11c+ DC cell (CD11c positive dendritic cells)
CD19+ B cell line (CD19+ human B lymphoma cells)
CD4+ T cell line (A T-helper cell)
DX5+ NK cell line (Unique subsets of NK cells in mouse liver)
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Positive ES cell clones were expanded and injected into C57BL/6J blastocysts to generate the chimeric offspring. The chimeric mice were mated with C57BL/6J mice to obtain the lnc-Dpf3 floxed heterozygous mouse (lnc-Dpf3fl/+). The lnc-Dpf3fl/+ mice were bred with C57BL/6J mice expressing the Cre recombinase under the control of the Itgax promoter (Itgax-cre mice; The Jackson Laboratory) to generate lnc-Dpf3 floxed heterozygous mouse with Itgax-cre allele (lnc-Dpf3fl/+Itgax-cre+). These mice were intercrossed to generate DC-specific lnc-Dpf3-deficient mice (lnc-Dpf3fl/flItgax-cre+) used for this study. Hif1afl/fl mice, a kindly gift from Dr. Ming Zhang (Renji Hospital, Medical College of Shanghai Jiaotong University, China) were crossed with Itgax-cre mice to generate DC-specific HIF-1-Alpha-deficient mice (Hif1afl/flItgax-cre+). All mice were maintained under specific pathogen-free conditions and used at 6-8 weeks of age.
MAP kinase kinase 4 (MAP2K4)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary YTHDF2 knockdown increases mRNA expression levels of MAP kinase kinase 4 (MAP2K4) and MAP4K4 via stabilizing the mRNA transcripts, which activate MAPK and NF-Kappa-B signaling pathways, which promote the expression of proinflammatory cytokines and aggravate the inflammatory response in LPS-stimulated RAW 264.7 cells.
Responsed Disease Inflammatory response [ICD-11: MG46]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Pathway Response MAPK signaling pathway hsa04010
In-vitro Model RAW 264.7 Mouse leukemia Mus musculus CVCL_0493
Mothers against decapentaplegic homolog 7 (SMAD7)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Mothers against decapentaplegic homolog 7 (SMAD7) and Smurf1 mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.
Responsed Disease Inflammatory response [ICD-11: MG46]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Pathway Response MAPK signaling pathway hsa04010
Cell Process RNA stability
In-vitro Model MC3T3-E1 Normal Mus musculus CVCL_0409
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Mothers against decapentaplegic homolog 7 (SMAD7) and Smurf1 mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.
Responsed Disease Inflammatory response [ICD-11: MG46]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Pathway Response MAPK signaling pathway hsa04010
Cell Process RNA stability
In-vitro Model MC3T3-E1 Normal Mus musculus CVCL_0409
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Disease
In total 18 item(s) under this disease
Crosstalk ID: M6ACROT03014
m6A Regulator YTH domain-containing family protein 2 (YTHDF2)
m6A Target Lysine-specific demethylase 6B (KDM6B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT03015
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Lysine-specific demethylase 6B (KDM6B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT03016
m6A Regulator Methyltransferase-like 14 (METTL14)
m6A Target Lysine-specific demethylase 6B (KDM6B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT03017
m6A Regulator Wilms tumor 1-associating protein (WTAP)
m6A Target Interleukin-6 (IL-6)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03018
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Interleukin-6 (IL-6)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03019
m6A Regulator Methyltransferase-like 14 (METTL14)
m6A Target Interleukin-6 (IL-6)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03149
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Programmed cell death 1 ligand 1 (CD274/PD-L1)
Epigenetic Regulator Histone-lysine N-methyltransferase EHMT2 (EHMT2)
Regulated Target Histone H3 lysine 9 dimethylation (H3K9me2)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03150
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target CX3C chemokine receptor 1 (CX3CR1)
Epigenetic Regulator Histone-lysine N-methyltransferase EHMT2 (EHMT2)
Regulated Target Histone H3 lysine 9 dimethylation (H3K9me2)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03151
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Caspase-1 (CASP1)
Epigenetic Regulator Histone-lysine N-methyltransferase EHMT2 (EHMT2)
Regulated Target Histone H3 lysine 9 dimethylation (H3K9me2)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03491
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Protein SON
Epigenetic Regulator Histone-lysine N-methyltransferase EHMT2 (EHMT2)
Regulated Target Histone H3 lysine 9 dimethylation (H3K9me2)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT03492
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Protein-tyrosine kinase 2-beta (PYK2)
Epigenetic Regulator Histone-lysine N-methyltransferase EHMT2 (EHMT2)
Regulated Target Histone H3 lysine 9 dimethylation (H3K9me2)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT05173
m6A Regulator Methyltransferase-like 14 (METTL14)
m6A Target C-X-C chemokine receptor type 4 (CXCR4)
Epigenetic Regulator hsa_circ_0125169 (Circ_METTL14(11)S)
Regulated Target Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship ncRNA → m6A
Crosstalk ID: M6ACROT05995
m6A Regulator YTH domain-containing family protein 2 (YTHDF2)
m6A Target Lysine-specific demethylase 6B (KDM6B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT05996
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Lysine-specific demethylase 6B (KDM6B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT05997
m6A Regulator Methyltransferase-like 14 (METTL14)
m6A Target Lysine-specific demethylase 6B (KDM6B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship m6A → Histone modification
Crosstalk ID: M6ACROT05998
m6A Regulator Wilms tumor 1-associating protein (WTAP)
m6A Target Interleukin-12 subunit beta (IL12B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT05999
m6A Regulator Methyltransferase-like 3 (METTL3)
m6A Target Interleukin-12 subunit beta (IL12B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship Histone modification → m6A
Crosstalk ID: M6ACROT06000
m6A Regulator Methyltransferase-like 14 (METTL14)
m6A Target Interleukin-12 subunit beta (IL12B)
Epigenetic Regulator Lysine-specific demethylase 6B (KDM6B)
Regulated Target Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship Histone modification → m6A
References
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Ref 2 METTL3 Regulates Osteoblast Differentiation and Inflammatory Response via Smad Signaling and MAPK Signaling. Int J Mol Sci. 2019 Dec 27;21(1):199. doi: 10.3390/ijms21010199.
Ref 3 RNA-binding protein YTHDF3 suppresses interferon-dependent antiviral responses by promoting FOXO3 translation. Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):976-981. doi: 10.1073/pnas.1812536116. Epub 2018 Dec 27.
Ref 4 m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response. Int J Mol Sci. 2019 Mar 15;20(6):1323. doi: 10.3390/ijms20061323.
Ref 5 CCR7 Chemokine Receptor-Inducible lnc-Dpf3 Restrains Dendritic Cell Migration by Inhibiting HIF-1Alpha-Mediated Glycolysis. Immunity. 2019 Mar 19;50(3):600-615.e15. doi: 10.1016/j.immuni.2019.01.021. Epub 2019 Feb 26.
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Ref 8 Interplay of m(6)A and H3K27 trimethylation restrains inflammation during bacterial infection. Sci Adv. 2020 Aug 19;6(34):eaba0647. doi: 10.1126/sciadv.aba0647. eCollection 2020 Aug.
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Ref 10 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. Blood. 2006 Mar 1;107(5):2184-91. doi: 10.1182/blood-2005-06-2317. Epub 2005 Oct 27.
Ref 11 Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther. 2005 May;77(5):404-14. doi: 10.1016/j.clpt.2004.12.266.