Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05519
[1]
m6A modification DLEU2 DLEU2 FTO Demethylation : m6A sites Direct Inhibition Non-coding RNA LINC00022 CDKN1A  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Fat mass and obesity-associated protein (FTO) ERASER
m6A Target Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022) LncRNA View Details
Regulated Target Cyclin-dependent kinase inhibitor 1 (CDKN1A) View Details
Crosstalk Relationship m6A  →  ncRNA Inhibition
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary The elevated FTO in esophageal squamous cell carcinoma decreased m6A methylation of Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022) transcript, leading to the inhibition of LINC00022 decay via the m6A reader YTHDF2. LINC00022 directly binds to Cyclin-dependent kinase inhibitor 1 (CDKN1A) protein and promotes its ubiquitination-mediated degradation, thereby facilitating cell-cycle progression and proliferation.
Responsed Disease Esophageal Squamous Cell Carcinoma ICD-11: 2B70.1
Cell Process Ubiquitination degradation
Cell cycle
Cell proliferation.
In-vitro Model
KYSE-150 Esophageal squamous cell carcinoma Homo sapiens CVCL_1348
TE1
N.A. Mus musculus CVCL_C6K3
KYSE-70 Esophageal squamous cell carcinoma Homo sapiens CVCL_1356
KYSE-450 Esophageal squamous cell carcinoma Homo sapiens CVCL_1353
HET-1A Normal Homo sapiens CVCL_3702
In-vivo Model The number of cells inoculated in each mouse was 4 × 106, 1 × 106, 2 × 106 and 1 × 106, respectively.
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]
External Link
 Compound Name Nivolumab Approved [2]
External Link
 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
    Click to Show/Hide
External Link
 Compound Name Golnerminogene pradenovac Phase 3 [4]
Synonyms
TNFerade (TN)
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External Link
 Compound Name DKN-01 Phase 2 [5]
External Link
 Compound Name Pegamotecan Phase 2 [6]
Synonyms
Prothecan; EZ-246; PEG-camptothecin; PEG-camptothecin, Enzon; Polyethylene glycol-camptothecin, Enzon
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External Link
 Compound Name APR-246 Phase 2 [2]
Synonyms
Eprenetapopt
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External Link
 Compound Name Opdivo + Yervoy Phase 3 [2]
External Link
 Compound Name Anti-NY-ESO-1 CAR-T cells Phase 1/2 [7]
External Link
 Compound Name Anti-MUC1 CAR-T cells Phase 1/2 [8]
External Link
 Compound Name CAR-T Cells targeting EpCAM Phase 1/2 [9]
External Link
 Compound Name PCA062 Phase 1 [2]
External Link
 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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External Link
 Compound Name Ramorelix Discontinued in Phase 1 [11]
Synonyms
Hoe-013
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References
Ref 1 RNA m6A demethylase FTO-mediated epigenetic up-regulation of LINC00022 promotes tumorigenesis in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2021 Sep 20;40(1):294. doi: 10.1186/s13046-021-02096-1.
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)