m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00664
 [1], [2], [3], [4]
m6A modification MIR1246 MIR1246 METTL3 Methylation : m6A sites Indirect Enhancement RNA modification IL6 IL6 WDR4 Methylation : modification sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target microRNA 1246 (MIR1246)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> N7-methylguanosine (m7G)
Epigenetic Regulator tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4 (WDR4) WRITER View Details
Regulated Target Interleukin 6 (IL6) View Details
Crosstalk Relationship m6A  →  m7G Enhancement
Crosstalk Mechanism m6A modification indirectly impacts RNA modification through downstream signaling pathways
Crosstalk Summary METTL3 interacts with microRNA 1246 (MIR1246), increasing its m6A level and promoting its physical interaction with Interleukin 6 (IL6), which was regulated by WDR4-mediated m7G modification.
In-vitro Model
 HCT 116 Colon carcinoma Homo sapiens CVCL_0291
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Interleukin 6 (IL6) 15 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Siltuximab Approved [5]
External Link
TTD: D07NJN
 Compound Name Olokizumab Phase 3 [6]
MOA Modulator
External Link
TTD: D00NUG
 Compound Name Ziltivekimab Phase 3 [7]
MOA Inhibitor
External Link
TTD: DF86OC
 Compound Name RG6179 Phase 3 [8]
External Link
TTD: DWJM12
 Compound Name Sirukumab Phase 3 [9]
MOA Inhibitor
External Link
TTD: D01XVF
 Compound Name Clazakizumab Phase 2 [9]
MOA Inhibitor
External Link
TTD: D04RMM
 Compound Name CDP-6038 Phase 2 [10]
MOA Modulator
External Link
TTD: D07TCS
 Compound Name ALD-518 Phase 2 [10]
MOA Modulator
External Link
TTD: D0N0BW
 Compound Name YSIL6 Phase 2 [11]
MOA Inhibitor
External Link
TTD: D0VS2W
 Compound Name PF-04236921 Phase 2 [9]
MOA Inhibitor
External Link
TTD: D06NXG
 Compound Name Gerilimzumab Phase 1 [9]
External Link
TTD: D07IVS
 Compound Name MEDI5117 Phase 1 [12]
MOA Modulator
External Link
TTD: D0DT8Y
 Compound Name C326 Phase 1 [13]
MOA Inhibitor
External Link
TTD: D0GJ1U
 Compound Name OP-R003 Phase 1 [14]
Synonyms
VX-30; OP-R003-1; Elsilimomab derivative (hematological disease), OPi/Vaccinex; IL-6 antibodies (hematological disease), EUSA; IL6 antibodies (hematological disease), OPi/Vaccinex; OP-R003 (hematological cancer), GSK; OP-R003 (inflammation), GSK; Anti-IL-6 human MAb (hematological cancer), GSK; Anti-IL-6 human MAb(inflammation), GSK
    Click to Show/Hide
MOA Modulator
External Link
TTD: D0OK5R
 Compound Name SAR444419 Phase 1 [15]
External Link
TTD: DKX8W5
References
Ref 1 Multilevel defects in the hematopoietic niche in essential thrombocythemia. Haematologica. 2020 Mar;105(3):661-673. doi: 10.3324/haematol.2018.213686. Epub 2019 Jul 9.
Ref 2 Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway. J Exp Clin Cancer Res. 2019 Sep 6;38(1):393. doi: 10.1186/s13046-019-1408-4.
Ref 3 MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting paternally expressed gene 3. Mol Ther Nucleic Acids. 2021 Feb 24;24:542-553. doi: 10.1016/j.omtn.2021.02.020. eCollection 2021 Jun 4.
Ref 4 Exosomal miR-1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance. IUBMB Life. 2019 Dec;71(12):2020-2030. doi: 10.1002/iub.2147. Epub 2019 Aug 21.
Ref 5 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81. doi: 10.1038/nrd4545.
Ref 6 Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Ann Rheum Dis. 2014 September; 73(9): 1607-1615.
Ref 7 IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021 May 29;397(10289):2060-2069.
Ref 8 Clinical pipeline report, company report or official report of Roche
Ref 9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 10 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005 Aug;86(2):127-41. doi: 10.1016/j.ygeno.2005.04.008.
Ref 11 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020380)
Ref 12 Whole-molecule antibody engineering: generation of a high-affinity anti-IL-6 antibody with extended pharmacokinetics. J Mol Biol. 2011 Aug 26;411(4):791-807. doi: 10.1016/j.jmb.2011.06.031. Epub 2011 Jun 23.
Ref 13 The molecular basis of hepcidin-resistant hereditary hemochromatosis. Blood. 2009 Jul 9;114(2):437-43.
Ref 14 A high-affinity fully human anti-IL-6 mAb (OP-R003-1, 1339) for the treatment of Multiple Myeloma
Ref 15 Clinical pipeline report, company report or official report of Sanofi