Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03106
[1]
Histone modification H3K18la Epigenetic Regulator AP001885.4 Indirect Enhancement m6A modification MYC MYC METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target Myc proto-oncogene protein (MYC)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Regulated Target Histone H3 lysine 18 lactylation (H3K18la) View Details
Downstream Gene AP001885.4 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism Histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary AP001885.4 was overexpressed in ESCC cells because of a higher Histone H3 lysine 18 lactylation (H3K18la) level in the promoter and amplification, then enhanced histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc eventually upregulated Myc proto-oncogene protein (MYC) and promoted cell proliferation
Responsed Disease Esophageal Squamous Cell Carcinoma ICD-11: 2B70.1
Cell Process Cell proliferation
Cell colony formation
mRNA stability
In-vitro Model
Eca-109 Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
KYSE-510 Esophageal squamous cell carcinoma Homo sapiens CVCL_1354
KYSE-450 Esophageal squamous cell carcinoma Homo sapiens CVCL_1353
KYSE-410 Esophageal squamous cell carcinoma Homo sapiens CVCL_1352
KYSE-150 Esophageal squamous cell carcinoma Homo sapiens CVCL_1348
KYSE-140 Esophageal squamous cell carcinoma Homo sapiens CVCL_1347
KYSE-70 Esophageal squamous cell carcinoma Homo sapiens CVCL_1356
KYSE-30 Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Myc proto-oncogene protein (MYC) 3 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name AVI-5126 Phase 2 [2]
Synonyms
Resten-CP; NeuGene (CABG), AVI
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 Compound Name Resten-NG Phase 2 [3]
Synonyms
Resten-NG (TN)
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External Link
 Compound Name TWS-119 Investigative [4]
Synonyms
TWS119; 601514-19-6; 3-[[6-(3-Aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenol; TWS 119; GSK inhibitor XII; GSK-3beta Inhibitor XII, TWS119; Neurogenesis Inducer, TWS119; CHEMBL405759; 3-(6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenol; 3-((6-(3-AMINOPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)OXY)PHENOL; 3-{[6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy}phenol; Phenol, 3-[[6-(3-aminophenyl)-1H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]-; K00245; MLS006011018; GTPL5980; SCHEMBL5559045; GSK-3BETA INHIB
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External Link
2B70: Esophageal cancer 15 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Pembrolizumab Approved [5]
External Link
 Compound Name Nivolumab Approved [5]
External Link
 Compound Name Claudiximab Phase 3 [6]
Synonyms
IMAB-362; Anti-GC182 mAbs (cancer), Ganymed; Anti-GC182 monoclonal antibodies (cancer), Ganymed; Anti-CLDN18-2 mAbs (cancer), Ganymed; Anti-CLDN18-2 monoclonal antibodies (cancer), Ganymed
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External Link
 Compound Name Golnerminogene pradenovac Phase 3 [7]
Synonyms
TNFerade (TN)
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External Link
 Compound Name DKN-01 Phase 2 [8]
External Link
 Compound Name Pegamotecan Phase 2 [9]
Synonyms
Prothecan; EZ-246; PEG-camptothecin; PEG-camptothecin, Enzon; Polyethylene glycol-camptothecin, Enzon
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 Compound Name APR-246 Phase 2 [5]
Synonyms
Eprenetapopt
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 Compound Name Opdivo + Yervoy Phase 3 [5]
External Link
 Compound Name Anti-NY-ESO-1 CAR-T cells Phase 1/2 [10]
External Link
 Compound Name Anti-MUC1 CAR-T cells Phase 1/2 [11]
External Link
 Compound Name CAR-T Cells targeting EpCAM Phase 1/2 [12]
External Link
 Compound Name PCA062 Phase 1 [5]
External Link
 Compound Name Cellspan esophageal implant Clinical trial [5]
External Link
 Compound Name PKI166 Discontinued in Phase 2 [13]
Synonyms
PKI-166; CGP-75166; 187724-61-4; NVP-PKI166; CHEMBL1914653; AC1OCFE0; UNII-9RIE5HW38P; 9RIE5HW38P; SCHEMBL177814; GTPL7642; CHEMBL1963502; ZINC23255; AOB1619; PKI-75166; BDBM50358046; NCGC00387215-02; AS-16676; KB-275097; PKI-166, > 4-[4-[[(1R)-1-phenylethyl]amino]-7H-pyrrolo[4,5-e]pyrimidin-6-yl]phenol
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External Link
 Compound Name Ramorelix Discontinued in Phase 1 [14]
Synonyms
Hoe-013
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External Link
References
Ref 1 AP001885.4 promotes the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-kappaB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc. Anim Cells Syst (Seoul). 2024 Nov 1;28(1):536-550. doi: 10.1080/19768354.2024.2417458. eCollection 2024.
Ref 2 Efficacy of a phosphorodiamidate morpholino oligomer antisense compound in the inhibition of corneal transplant rejection in a rat cornea transplant model. J Ocul Pharmacol Ther. 2012 Apr;28(2):194-201. doi: 10.1089/jop.2011.0135. Epub 2011 Dec 7.
Ref 3 Local delivery of c-myc neutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affects vascular remodeling in the rabbit balloon injury model. Catheter Cardiovasc Interv. 2001 Oct;54(2):247-56. doi: 10.1002/ccd.1277.
Ref 4 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.
Ref 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6 ClinicalTrials.gov (NCT01197885) Efficacy and Safety Study of Multiple Doses of IMAB362 in Patients With Advanced Gastroesophageal Cancer. U.S. National Institutes of Health.
Ref 7 ClinicalTrials.gov (NCT00051467) A Study of TNFerade Biologic With 5-FU and Radiation Therapy for First-Line Treatment of Unresectable Locally Advanced Pancreatic Cancer. U.S. National Institutes of Health.
Ref 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 9 ClinicalTrials.gov (NCT00080002) Efficacy of Pegamotecan (PEG-Camptothecin) in Localized or Metastatic Cancer of the Stomach or Gastroesophageal Junction. U.S. National Institutes of Health.
Ref 10 ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
Ref 11 ClinicalTrials.gov (NCT03706326) CAR T and PD-1 Knockout Engineered T Cells for Esophageal Cancer
Ref 12 ClinicalTrials.gov (NCT03013712) A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer
Ref 13 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: 7642).
Ref 14 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008630)