m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03041
 [1]
m6A modification RNF40 RNF40 ALKBH5 Demethylation : m6A sites Direct Enhancement Histone modification H2AK119ub RNF40 Downstream Gene
m6A Modification:
m6A Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
m6A Target E3 ubiquitin-protein ligase BRE1B (RNF40)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator E3 ubiquitin-protein ligase BRE1B (RNF40) WRITER View Details
Regulated Target Histone H2A lysine 119 ubiquitination (H2AK119ub) View Details
Crosstalk Relationship m6A  →  Histone modification Enhancement
Crosstalk Mechanism m6A modification impacts directly histone modification through modulating the expression level of histone-associated enzymes
Crosstalk Summary RNA demethylase ALKBH5 upregulates USP22 and E3 ubiquitin-protein ligase BRE1B (RNF40) to inhibit Histone H2A lysine 119 ubiquitination (H2AK119ub) and induces expression of key replication and DNA repair-associated genes, driving osteosarcoma progression.
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Proteasome pathway degradation
In-vitro Model
 143B Osteosarcoma Homo sapiens CVCL_2270
U2OS Osteosarcoma Homo sapiens CVCL_0042
SaOS-2 Osteosarcoma Homo sapiens CVCL_0548
hFOB 1.19 Normal Homo sapiens CVCL_3708
In-vivo Model For tumor xenograft studies, 143B cells stably expressing scrambled shRNA or ALKBH5 shRNA (1 × 106) were injected subcutaneously into the flanks of 4-week-old athymic nude mice (n = 8/group; purchased from Envigo, Inc.). For orthotopic xenograft and experimental metastasis models, 143B cells stably expressing GFP-luc and scrambled shRNA or ALKBH5 shRNA (1 × 106) were injected into tibia or via tail vein, respectively, of 4-week-old athymic nude mice. Equal numbers of male and female mice were used. Tumor volumes and body weight were measured twice a week. Tumor volumes for subcutaneous injection model were measured using caliper and for intratibial and experimental metastasis models using Xenogen in vivo imaging system.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2B51: Osteosarcoma 12 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Cisplatin Approved [2]
Synonyms
Abiplatin; Biocisplatinum; Briplatin; Cismaplat; Cisplatine; Cisplatino; Cisplatinum; Cisplatyl; Citoplationo; Lederplatin; Neoplatin; Plastin; Platamine; Platidiam; Platinoxan; Randa; Cis-DDP; Cis-Diamminedichloroplatinum; Peyrone's chloride; Peyrone's salt; Cis-Dichlorodiammineplatinum(II); Cis-[PtCl2(NH3)2]; Cis-diamminedichloridoplatinum(II); Trans-diamminedichloridoplatinum(II); (SP-4-1)-diamminedichloridoplatinum; (SP-4-1)-diamminedichloroplatinum; (SP-4-2)-diamminedichloridoplatinum; (SP-4-2)-diamminedichloroplatinum; Cisplatin (Chemotherapy)
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External Link
CID: 5702198
TTD: D0U5HU
 Compound Name Naxitamab Phase 2 [2]
External Link
TTD: D0HI5D
 Compound Name Tideglusib Phase 2 [3]
Synonyms
NP-031112; NP-12; NP031112; Tideglusib(NP-031112)
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External Link
CID: 11313622
TTD: D0UT7X
DrugBank: DB12129
 Compound Name Hu3F8 mAb Phase 2 [4]
External Link
TTD: D0R4UA
 Compound Name Saracatinib Phase 2 [5]
Synonyms
H8H; AZD-0530; Saracatinib, AZD-0530, AZD0530; N-(5-Chloro-1,3-benzodioxol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine
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External Link
CID: 10302451
TTD: D0M0XB
DrugBank: DB11805
 Compound Name ALMB-0168 Phase 1/2 [6]
External Link
TTD: DXAI94
 Compound Name AU101 Phase 1/2 [7]
External Link
TTD: D0T9JW
 Compound Name [153Sm]CycloSam Phase 1 [8]
External Link
TTD: D8W1DJ
 Compound Name GD2 T cells Phase 1 [9]
External Link
TTD: D0QB7N
 Compound Name Anti-GD2-CAR engineered T cells Phase 1 [10]
External Link
TTD: D09DND
 Compound Name Robatumumab Discontinued in Phase 2 [11]
External Link
TTD: D0X9RN
 Compound Name DG-8 Investigative [12]
Synonyms
DH-9; PPAR gamma agonists (osteosarcoma/ADPKD); PPAR gamma agonists (osteosarcoma/ADPKD), Chinese Academy of Sciences
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External Link
TTD: D0L3VC
References
Ref 1 M6A RNA Methylation Regulates Histone Ubiquitination to Support Cancer Growth and Progression. Cancer Res. 2022 May 16;82(10):1872-1889. doi: 10.1158/0008-5472.CAN-21-2106.
Ref 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 3 Evidence for irreversible inhibition of glycogen synthase kinase-3Beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904. doi: 10.1074/jbc.M111.306472. Epub 2011 Nov 18.
Ref 4 ClinicalTrials.gov (NCT02502786) Humanized Monoclonal Antibody 3F8 (Hu3F8) With Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in the Treatment of Recurrent Osteosarcoma.
Ref 5 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. (Ligand id: 7731).
Ref 6 ClinicalTrials.gov (NCT04886765) A Phase I/II, Multi-center, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of ALMB-0168 in Patients With Osteosarcoma. U.S.National Institutes of Health.
Ref 7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 8 ClinicalTrials.gov (NCT03612466) A Dose Finding Study of CycloSam Combined With External Beam Radiotherapy. U.S. National Institutes of Health.
Ref 9 ClinicalTrials.gov (NCT01953900) iC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma and Neuroblastoma
Ref 10 ClinicalTrials.gov (NCT02107963) A Phase I Trial of T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Children and Young Adults With GD2+ Solid Tumors
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 800027277)
Ref 12 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.