Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02009
[1]
m6A modification SATB2 SATB2 FXR1 : m6A sites Direct Enhancement DNA methylation TET1 SATB2
m6A Modification:
m6A Regulator RNA-binding protein FXR1 (FXR1) READER
m6A Target DNA-binding protein SATB2 (SATB2)
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 DNA-binding protein SATB2 (SATB2) 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 DNA-binding protein SATB2 (SATB2), RPIA, WNT7B, BCL6, 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]
External Link
 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)