Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT06010
[1]
m6A modification FAT4 FAT4 FXR1 : m6A sites Direct Enhancement DNA methylation TET1 FAT4
m6A Modification:
m6A Regulator RNA-binding protein FXR1 (FXR1) READER
m6A Target Protocadherin Fat 4 (FAT4)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator Methylcytosine dioxygenase TET1 (TET1) ERASER View Details
Regulated Target Protocadherin Fat 4 (FAT4) View Details
Crosstalk Relationship m6A  →  DNA methylation Enhancement
Crosstalk Mechanism m6A modification directly impacts DNA methylation through recruiting DNA methyltransferases or demethylases.
Crosstalk Summary Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. These gene include SATB2, RPIA, WNT7B, BCL6, Protocadherin Fat 4 (FAT4) and SAMD9L.
Responsed Disease Esophageal Squamous Cell Carcinoma ICD-11: 2B70.1
Cell Process Transcription
Cell proliferation
Cell migration
Cell invasion
In-vitro Model
HEK293T Normal Homo sapiens CVCL_0063
KYSE-30 Esophageal squamous cell carcinoma Homo sapiens CVCL_1351
KYSE-510 Esophageal squamous cell carcinoma Homo sapiens CVCL_1354
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 [2]
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 Compound Name Nivolumab Approved [2]
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 Compound Name Claudiximab Phase 3 [3]
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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 Compound Name Golnerminogene pradenovac Phase 3 [4]
Synonyms
TNFerade (TN)
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 Compound Name DKN-01 Phase 2 [5]
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 Compound Name Pegamotecan Phase 2 [6]
Synonyms
Prothecan; EZ-246; PEG-camptothecin; PEG-camptothecin, Enzon; Polyethylene glycol-camptothecin, Enzon
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 Compound Name APR-246 Phase 2 [2]
Synonyms
Eprenetapopt
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 Compound Name Opdivo + Yervoy Phase 3 [2]
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 Compound Name Anti-NY-ESO-1 CAR-T cells Phase 1/2 [7]
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 Compound Name Anti-MUC1 CAR-T cells Phase 1/2 [8]
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 Compound Name CAR-T Cells targeting EpCAM Phase 1/2 [9]
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 Compound Name PCA062 Phase 1 [2]
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 Compound Name Cellspan esophageal implant Clinical trial [2]
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 Compound Name PKI166 Discontinued in Phase 2 [10]
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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 Compound Name Ramorelix Discontinued in Phase 1 [11]
Synonyms
Hoe-013
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References
Ref 1 RNA m(6)A regulates transcription via DNA demethylation and chromatin accessibility. Nat Genet. 2022 Sep;54(9):1427-1437. doi: 10.1038/s41588-022-01173-1. Epub 2022 Sep 7.
Ref 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 3 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 4 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 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6 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 7 ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
Ref 8 ClinicalTrials.gov (NCT03706326) CAR T and PD-1 Knockout Engineered T Cells for Esophageal Cancer
Ref 9 ClinicalTrials.gov (NCT03013712) A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer
Ref 10 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 11 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008630)