m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05466
 [1]
m6A modification hsa-mir-181b-1 hsa-mir-181b-1 ALKBH5 Demethylation : m6A sites Direct Inhibition Non-coding RNA miR-181b-1 YAP1  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
m6A Target hsa-mir-181b-1
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-mir-181b-1 microRNA View Details
Regulated Target Transcriptional coactivator YAP1 (YAP1) View Details
Crosstalk Relationship m6A  →  ncRNA Inhibition
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary ALKBH5 is an anti-tumor factor or a pro-apoptotic factor, acting at least partially by suppressing Transcriptional coactivator YAP1 (YAP1) expression through dual mechanisms with direct m6A methylation of YAP and indirect downregulation of YAP level due to methylation of hsa-mir-181b-1. Further results revealed that m6A methylated pre-miR-181b-1 was subsequently recognized by m6A-binding protein YTHDF2 to mediate RNA degradation. However, methylated YAP transcripts were recognized by YTHDF1 to promote its translation. ALKBH5 overexpression was considered a new approach of replacement therapy for osteosarcoma treatment.
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell growth
Cell migration
Cell invasion
Cell apoptosis
In-vitro Model
 U2OS Osteosarcoma Homo sapiens CVCL_0042
In-vivo Model Three-week-old BABL/c female nude mice were randomized into three groups. 5 × 106 143B cells were subcutaneously injected in mice, and the tumor volume was assessed every 2 weeks. Eight weeks after injection, the animals were killed. The xenograft tumors were harvested and the tumor volumes were calculated by the standard formula: length × width2/2.
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 ALKBH5 suppresses tumor progression via an m(6)A-dependent epigenetic silencing of pre-miR-181b-1/YAP signaling axis in osteosarcoma. Cell Death Dis. 2021 Jan 11;12(1):60. doi: 10.1038/s41419-020-03315-x.
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.