m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05203
 [1]
Non-coding RNA FTO-IT1 RBM15  lncRNA       miRNA   circRNA Direct Inhibition m6A modification FAS FAS RBM15 Methylation : m6A sites
m6A Modification:
m6A Regulator RNA-binding motif protein 15 (RBM15) WRITER
 Regulator Info 
m6A Target Tumor necrosis factor receptor superfamily member 6 (FAS)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator FTO intronic transcript 1 (FTO-IT1) LncRNA View Details
Regulated Target RNA binding motif protein 15 (RBM15) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary m6A RIP-seq analysis revealed that FTO-IT1 knockout increased mRNA m6A methylation of a subset of p53 transcriptional target genes (e.g., Tumor necrosis factor receptor superfamily member 6 (FAS), TP53INP1, and SESN2) and induced PCa cell cycle arrest and apoptosis. FTO-IT1 directly binds RBM15 and inhibits RBM15 binding, m6A methylation, and stability of p53 target mRNAs.
In-vitro Model
 HEK293T Normal Homo sapiens CVCL_0063
22Rv1 Prostate carcinoma Homo sapiens CVCL_1045
LNCaP C4-2 Prostate carcinoma Homo sapiens CVCL_4782
PC-3 Prostate carcinoma Homo sapiens CVCL_0035
LNCaP Prostate carcinoma Homo sapiens CVCL_0395
LAPC-4 Prostate carcinoma Homo sapiens CVCL_4744
In-vivo Model 5 × 106 of mock KO or FTO-IT1 KO C4-2R cells were mixed with Matrigel (50 μ l of PBS plus 50 μ l of Matrigel (BD Biosciences)) and injected subcutaneously into mice. For 22Rv1 xenografts, 5 × 106 of cells were mixed with Matrigel (50 μ l of PBS plus 50 μ l of Matrigel (BD Biosciences)) and injected subcutaneously into mice.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Tumor necrosis factor receptor superfamily member 6 (FAS) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name VB-111 Phase 3 [2]
MOA Modulator
External Link
TTD: D0S4LV
 Compound Name DE-098 Phase 2 [3]
Synonyms
ARG-098; Anti-Fas antibody, Santen; Anti-APO-1 antibody, Santen
    Click to Show/Hide
External Link
TTD: D07PRH
 Compound Name APG-101 Phase 2 [4]
Synonyms
CD95 receptor extracellular domain-IgG fused protein (GvHD), Apogenix; CD95 receptor extracellular domain-IgG fused protein (myocardial infarction), Apogenix; CD95 receptor extracellular domain-IgG fused protein (stroke), Apogenix; CD95 receptor extracellular domain-immunoglobulin G fused protein (graft versus hostdisease), Apogenix
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MOA Inhibitor
External Link
TTD: D0N4JI
 Compound Name APO-010 Phase 1 [5]
Synonyms
MegaFasL; Anticancer therapeutics (FasL), APoxis; Cancer therapeutics (FasL), Apoxis; Soluble FasL (Mega-Ligand), Apoxis; Soluble FasL (Mega-Ligand), TopoTarget
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MOA Binder
External Link
TTD: D0Q6SF
 Compound Name F61F12 Investigative [6]
Synonyms
Anti-Fas mAb (cancer), IMED
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External Link
TTD: D0N1DG
 Compound Name APG-103 Investigative [6]
Synonyms
CD95 receptor inhibitor (inflammatory disease), Apogenix
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MOA Inhibitor
External Link
TTD: D0QA7X
 Compound Name 2-aminophenoxazine-3-one Investigative [7]
Synonyms
Questiomycin A; 2-Amino-3H-phenoxazin-3-one; 2-Aminophenoxazin-3-one; 1916-59-2; 2-Aminophenoxazon; 2-Aminophenoxazone; 3-Aminophenoxazone; 2-Amino-3-phenoxazone; 3H-Phenoxazin-3-one, 2-amino-; Isophenoxazine; 2-amino-phenoxazin-3-one; NSC 94945; MLS000736964; CHEBI:17293; SMR000528446; BRN 0014215; Questinomycine A; 3H-Phenoxazin-3-one,2-amino-; AV toxin C; 2-Aminophenoxazinone; Phx-3 cpd; Phx-3; 2-amino-3-phenoxazinone; 2-azanylphenoxazin-3-one; Acrospermum viticola toxin C; NCIOpen2_006212; 4-27-00-05519 (Beilstein Handbook Reference); cid_72725; CHEMBL146710; SCHEMBL2609261; BDBM76155; DTXSID60172691; HMS2270F19; NSC94945; ZINC4095812; MFCD00207317; NSC-94945; 2-acetylamino-(3h)-phenoxazin-3-one; AKOS027339724; NCGC00246903-01; AS-47041; C02161; J-012388; BRD-K66640612-001-05-8; Q15424786
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MOA Activator
External Link
CID: 72725
TTD: DAQ31P
 Compound Name ISIS 17020 Investigative [8]
External Link
TTD: D0J1SU
References
Ref 1 A lncRNA from the FTO locus acts as a suppressor of the m(6)A writer complex and p53 tumor suppression signaling. Mol Cell. 2023 Aug 3;83(15):2692-2708.e7. doi: 10.1016/j.molcel.2023.06.024. Epub 2023 Jul 20.
Ref 2 Phase I dose-escalation study of VB-111, an antiangiogenic virotherapy, in patients with advanced solid tumors. Clin Cancer Res. 2013 Jul 15;19(14):3996-4007. doi: 10.1158/1078-0432.CCR-12-2079. Epub 2013 Apr 15.
Ref 3 ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model. BMC Musculoskeletal Disorders 2010,11:221.
Ref 4 Pharmacokinetics, pharmacodynamics, safety and tolerability of APG101, a CD95-Fc fusion protein, in healthy volunteers and two glioma patients. Int Immunopharmacol. 2012 May;13(1):93-100. doi: 10.1016/j.intimp.2012.03.004. Epub 2012 Mar 21.
Ref 5 APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo. Neuro Oncol. 2011 Feb;13(2):155-64. doi: 10.1093/neuonc/noq176. Epub 2010 Dec 22.
Ref 6 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1875).
Ref 7 Apoptosis as a mechanism for the treatment of adult T cell leukemia: promising drugs from benchside to bedside. Drug Discov Today. 2020 Jul;25(7):1189-1197. doi: 10.1016/j.drudis.2020.04.023. Epub 2020 May 7.
Ref 8 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.