m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03376
 [1], [2]
Histone modification H3K18la Epigenetic Regulator AP001885.4 Indirect Enhancement m6A modification NR4A2 NR4A2 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Nuclear receptor subfamily 4 group A member 2 (NR4A2)
 Targert Gene 
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 c-myc and promoted cell proliferation ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on Nuclear receptor subfamily 4 group A member 2 (NR4A2) expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival.
Responsed Disease Esophageal Squamous Cell Carcinoma ICD-11: 2B70.1
 Disease Info 
Responsed Drug celecoxib
 Drug Info 
Cell Process mRNA stability
Cell proliferation
In-vitro Model
 KYSE-150 Esophageal squamous cell carcinoma Homo sapiens CVCL_1348
Eca-109 Esophageal squamous cell carcinoma Homo sapiens CVCL_6898
KYSE-450 Esophageal squamous cell carcinoma Homo sapiens CVCL_1353
KYSE-30 Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
HET-1A Normal Homo sapiens CVCL_3702
HEK293T Normal Homo sapiens CVCL_0063
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2B70: Esophageal cancer 15 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Pembrolizumab Approved [3]
External Link
TTD: D08ANZ
 Compound Name Nivolumab Approved [3]
External Link
TTD: D00GOV
 Compound Name Claudiximab Phase 3 [4]
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
    Click to Show/Hide
External Link
TTD: D0B3ZC
 Compound Name Golnerminogene pradenovac Phase 3 [5]
Synonyms
TNFerade (TN)
    Click to Show/Hide
External Link
TTD: D03QBT
 Compound Name DKN-01 Phase 2 [6]
External Link
TTD: DMF73Z
 Compound Name Pegamotecan Phase 2 [7]
Synonyms
Prothecan; EZ-246; PEG-camptothecin; PEG-camptothecin, Enzon; Polyethylene glycol-camptothecin, Enzon
    Click to Show/Hide
External Link
CID: 11297617
TTD: D0D4CX
 Compound Name APR-246 Phase 2 [3]
Synonyms
Eprenetapopt
    Click to Show/Hide
External Link
CID: 52918385
TTD: D03XTY
DrugBank: DB11684
 Compound Name Opdivo + Yervoy Phase 3 [3]
External Link
TTD: D02VYE
 Compound Name Anti-NY-ESO-1 CAR-T cells Phase 1/2 [8]
External Link
TTD: D0LJ2S
 Compound Name Anti-MUC1 CAR-T cells Phase 1/2 [9]
External Link
TTD: D09KWN
 Compound Name CAR-T Cells targeting EpCAM Phase 1/2 [10]
External Link
TTD: D08QYW
 Compound Name PCA062 Phase 1 [3]
External Link
TTD: D09WSR
 Compound Name Cellspan esophageal implant Clinical trial [3]
External Link
TTD: D0SW1D
 Compound Name PKI166 Discontinued in Phase 2 [11]
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
    Click to Show/Hide
External Link
CID: 6918403
TTD: D07GFF
 Compound Name Ramorelix Discontinued in Phase 1 [12]
Synonyms
Hoe-013
    Click to Show/Hide
External Link
CID: 25077455
TTD: D0S6AQ
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 Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma. Cell Death Differ. 2024 May;31(5):558-573. doi: 10.1038/s41418-024-01285-7. Epub 2024 Apr 3.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 4 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 5 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 6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 7 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 8 ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
Ref 9 ClinicalTrials.gov (NCT03706326) CAR T and PD-1 Knockout Engineered T Cells for Esophageal Cancer
Ref 10 ClinicalTrials.gov (NCT03013712) A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer
Ref 11 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 12 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008630)