Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05038
[1], [2]
Non-coding RNA miR-145 YTHDF2  lncRNA       miRNA   circRNA Direct Inhibition m6A modification POU5F1 POU5F1 YTHDF2 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
m6A Target POU domain, class 5, transcription factor 1 (POU5F1)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator MicroRNA 145 (MIR145) microRNA View Details
Regulated Target YTH domain-containing family protein 2 (YTHDF2) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary MIR145 modulates m6A levels by targeting the 3'-UTR of YTHDF2 mRNA in HCC cells.YTHDF2 promotes the CSC liver phenotype and cancer metastasis by modulating the m6A methylation of POU domain, class 5, transcription factor 1 (POU5F1) mRNA. YTHDF2 expression is positively correlated with OCT4 expression and m6A levels in the 5'-UTR of OCT4 mRNA in clinical hepatocellular carcinoma specimens.
Responsed Disease Liver cancer ICD-11: 2C12
Pathway Response RNA degradation hsa03018
Cell Process Cancer metastasis
In-vitro Model
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2C12: Liver cancer 49 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name 90Y-loaded resin microspheres Approved [3]
External Link
 Compound Name Thymalfasin Phase 2 [4]
Synonyms
Zadaxin; 62304-98-7; Thymosin alpha1; Thymosin alpha 1; Thymosin alpha1 (ox); Thymosin alpha1 (human); Thymalfasin [USAN:INN]; UNII-W0B22ISQ1C; Thymosin-alpha-1; 69440-99-9; Thymosin alpha1 (cattle); C129H215N33O55; W0B22ISQ1C; Zadaxin (TN); Thymalfasin alfa 1
    Click to Show/Hide
External Link
 Compound Name Ferumoxides Approved [5]
Synonyms
AMI-25; 119683-68-0; Feridex; Feridex IV; Superparamagnetic iron oxide; UNII-G6N3J05W84; Ferumoxides [USAN:USP:BAN]; CCRIS 6722; HSDB 8072; AC1O5DID; G6N3J05W84; iron(2+); iron(3+); Iron oxide crystal is inverse spinel (X-ray data); Fe(II) and Fe(III) are present (Mossbauer Spectroscopy; Physical form is a colloidal particle of nonstoichiometric
    Click to Show/Hide
External Link
 Compound Name DTI-015 Approved [6]
Synonyms
Carmustine; 154-93-8; 1,3-Bis(2-chloroethyl)-1-nitrosourea; BCNU; Carmustin; Nitrumon; Carmubris; Gliadel; BiCNU; Bi CNU; Carmustinum; Bischlorethylnitrosurea; Bischlorethylnitrosourea; Carmustina; Becenun; Becenum; Bischloroethyl nitrosourea; N,N'-BIS(2-CHLOROETHYL)-N-NITROSOUREA; Bis(2-chloroethyl)nitrosourea; Urea, N,N'-bis(2-chloroethyl)-N-nitroso-; Gliadel Wafer; FDA 0345; Bischloroethylnitrosourea; SRI 1720; 1,3-Bis(2-chloroethyl)nitrosourea; BiCNU (TN); Carmustinum [INN-Latin]; Carmustina [INN-Spanish]; DTI 015; NCI-C04773; SK; Injectable carmustine, Direct Therapeutics
    Click to Show/Hide
External Link
 Compound Name Nofazinlimab Phase 3 [7]
Synonyms
CS1003; EQ176
    Click to Show/Hide
External Link
 Compound Name PV-10 Phase 3 [8]
Synonyms
632-69-9; Rose bengal sodium; Rose bengal disodium salt; R105 sodium; Rose-bengal (131 I) natrium; Food Red No 105, sodium salt; EINECS 211-183-3; Food Red Color No 105, sodium salt; Sel disodique de rose bengale iodee (131 I); Rose bengale (131 I) sodique [INN-French]; Rosa bengala sodica (131 I) [INN-Spanish]; Roseum bengalense (131 I) natricum [INN-Latin]; 2,4,5,7-Tetraido(m,p,o',m')tetrachlorofluorescein, disodium salt; Fluorescein, 4,5,6,7-tetrachloro-2',4',5',7'-tetraiodo-, disodium salt; Disodium
    Click to Show/Hide
External Link
 Compound Name Brivanib Phase 3 [9]
Synonyms
649735-46-6; BMS-540215; Brivanib (BMS-540215); BMS 540215; UNII-DDU33B674I; Brivanib [USAN]; BMS540215; DDU33B674I; CHEMBL377300; (2R)-1-[4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]propanol; Brivanib (USAN); (2R)-1-[4-[(4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY]-5-METHYL-PYRROLO[2,1-F][1,2,4]TRIAZIN-6-YL]OXYPROPAN-2-OL; (2R)-1-({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-ol
    Click to Show/Hide
External Link
 Compound Name JX-594 Phase 3 [10]
Synonyms
Pexastimogene devacirepvec
    Click to Show/Hide
External Link
 Compound Name ABH001 Phase 3 [11]
External Link
 Compound Name MTC-DOX Phase 2/3 [12]
Synonyms
MTC-doxorubicin
    Click to Show/Hide
External Link
 Compound Name KD018 Phase 2 [13]
External Link
 Compound Name Doxorubicin-eluting beads Phase 2 [14]
Synonyms
DC Bead (TN)
    Click to Show/Hide
External Link
 Compound Name 32-P BioSilicon Phase 2 [15]
Synonyms
BrachySil
    Click to Show/Hide
External Link
 Compound Name Cixutumumab Phase 2 [16]
Synonyms
LY3012217
    Click to Show/Hide
External Link
 Compound Name [131I]-Metuximab Phase 2 [17]
External Link
 Compound Name Darinaparsin Phase 2 [18]
Synonyms
ZIO-101
    Click to Show/Hide
External Link
 Compound Name Tigatuzumab Phase 2 [19]
External Link
 Compound Name CMC-001 Phase 2 [20]
Synonyms
Manganese-based MRI contrast agent (liver tumor imaging), CMC Contrast
    Click to Show/Hide
External Link
 Compound Name OBP-301 Phase 1/2 [21]
External Link
 Compound Name MBO7133 Phase 1/2 [22]
External Link
 Compound Name INCB62079 Phase 1/2 [8]
External Link
 Compound Name NV-1020 Phase 1/2 [23]
External Link
 Compound Name DCVax-Liver Phase 1/2 [24]
Synonyms
Dendritic cell-based immunotherapy (liver cancer), Northwest Biotherapeutics
    Click to Show/Hide
External Link
 Compound Name SRF388 Phase 1 [25]
External Link
 Compound Name ET140202 Phase 1 [26]
External Link
 Compound Name ADP-A2AFP Phase 1 [27]
External Link
 Compound Name SM04755 Phase 1 [28]
External Link
 Compound Name Anti-CEA CAR-T therapy Phase 1 [8]
External Link
 Compound Name PI-166 Phase 1 [29]
External Link
 Compound Name CRS-100 Phase 1 [30]
External Link
 Compound Name Autologous ET1402L1-CART cells Phase 1 [31]
External Link
 Compound Name Anti-CD133-CAR vector-transduced T cells Phase 1 [32]
External Link
 Compound Name MRX34 Phase 1 [33]
External Link
 Compound Name ALN-VSP Phase 1 [34]
External Link
 Compound Name EPCAM-targeted CAR-T cells Clinical trial [35]
External Link
 Compound Name ADI Discontinued in Phase 3 [36]
Synonyms
Arginine deiminase
    Click to Show/Hide
External Link
 Compound Name GN-1140 Discontinued in Phase 2 [37]
External Link
 Compound Name OGT-719 Discontinued in Phase 2 [38]
Synonyms
OGS-719
    Click to Show/Hide
External Link
 Compound Name AFP-Scan Discontinued in Phase 2 [39]
External Link
 Compound Name SR1078 Preclinical [40]
Synonyms
1246525-60-9; SR 1078; SR-1078; N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-4-(trifluoromethyl)benzamide; CHEMBL3094387; N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-4-(trifluoromethyl)benzamide; N-[4-[2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-4-(trifluoromethyl)benzamide; SCHEMBL4880524; C17H10F9NO2; DTXSID30591895; BCP09203; EX-A2215; 4063AH; BDBM50444350; s5775; ZINC98052696; AKOS024458390; CS-1045; NCGC00379222-02; AK547149; AS-55921; HY-14422; W-5797; SR-03000001078; SR-03000001078-1; SR-03000001078-2
    Click to Show/Hide
External Link
 Compound Name Occlusin Preclinical [41]
Synonyms
Occlusin 50 Injection; Occlusin 500 injection
    Click to Show/Hide
External Link
 Compound Name HRC-201 Terminated [42]
Synonyms
Hemoglobin-imaging conjugate (HepSelect), Hemosol
    Click to Show/Hide
External Link
 Compound Name 1,2,3,4,5,6-hexabromocyclohexane Investigative [43]
Synonyms
1837-91-8; Benzene hexabromide; Cyclohexane, 1,2,3,4,5,6-hexabromo-; Hexabromocyclohexane; JAK2 Inhibitor II; ACMC-1BQJT; SCHEMBL459442; trans-alpha-Benzene hexabromide; CHEMBL444236; DTXSID4052687; CHEBI:93940; NSC7908; HMS3268H22; HMS3413C10; HMS3677C10; NSC-7908; ZINC1586309; ANW-23174; MFCD00059127; s5902; Cyclohexane,2,3,4,5,6-hexabromo-; AKOS015836040; 1,2,3,4,5,6-Hexabromo-cyclohexane; 1,2,3,4,5,6-Hexabromocyclohexane #; NCGC00092358-01; NCGC00092358-02; 1,2,3,4,5,6-hexakis(bromanyl)cyclohexane; A4510; FT-0633875; JAK2 Inhibitor II - CAS 1837-91-8; 1,2,3,4,5,6-Hexabromocyclohexane;NSC7908; A812818; 1,2,3,4,5,6-Hexabrom-cyclohexan (I(2)-Form); J-011778; 1,2,3,4,5,6-Hexabromocyclohexane, >=98% (HPLC); BRD-K06817181-001-01-5; Q27165694
    Click to Show/Hide
External Link
 Compound Name STP-322 Investigative [44]
Synonyms
Multi-targeted siRNA therapeutic cocktail (nanoparticle, liver tumor), Sirnaomics
    Click to Show/Hide
External Link
 Compound Name AMB-8LK Investigative [44]
Synonyms
Cancer therapy (monoclonal antibody), MAT Biopharma; Y90 anti-ferritin monoclonal antibody (cancer), MAT Biopharma; Yttrium-90 anti-ferritin mAb (cancer), MAT Biopharma; Yttrium-90 anti-ferritin mAb (Hodgkin's disease/pancreatic/liver cancer), MAT Biopharma; 90Y-AMB8LK mAb (cancer), MAT Biopharma; 90Y-AMB8LK monoclonal antibody (cancer), MAT Biopharma; 90Y-labelled anti-ferritin monoclonal antibody (cancer), MAT Biopharma
    Click to Show/Hide
External Link
 Compound Name MiR-34a mimics Investigative [44]
Synonyms
MiR-34a mimics (liver cancer)
    Click to Show/Hide
External Link
 Compound Name P53 fusion protein Investigative [44]
Synonyms
P53 fusion protein (pancreatic/liver cancer)
    Click to Show/Hide
External Link
 Compound Name OP-05 Investigative [44]
Synonyms
OP-05 program (prodrug, liver tumor); OP-05 program (prodrug, liver tumor), Onco-Pharmakon
    Click to Show/Hide
External Link
 Compound Name GR-DD1 Investigative [44]
Synonyms
Cytotoxin (hepatic metastasis), ERYtech
    Click to Show/Hide
External Link
References
Ref 1 MicroRNA-145 Modulates N(6)-Methyladenosine Levels by Targeting the 3'-Untranslated mRNA Region of the N(6)-Methyladenosine Binding YTH Domain Family 2 Protein. J Biol Chem. 2017 Mar 3;292(9):3614-3623. doi: 10.1074/jbc.M116.749689. Epub 2017 Jan 19.
Ref 2 YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation. Oncogene. 2020 Jun;39(23):4507-4518. doi: 10.1038/s41388-020-1303-7. Epub 2020 May 4.
Ref 3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services.
Ref 4 ClinicalTrials.gov (NCT01031966) A Pilot Study to Evaluate ZADAXIN's (Thymalfasin) Ability to Enhance Immune Response to the H1N1sw Influenza Vaccine. U.S. National Institutes of Health.
Ref 5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 6 Carmustine-induced toxicity, DNA crosslinking and O6-methylguanine-DNA methyltransferase activity in two human lung cancer cell lines. Eur J Cancer. 1991;27(12):1658-62.
Ref 7 ClinicalTrials.gov (NCT04194775) A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC). 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 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: 5671).
Ref 10 ClinicalTrials.gov (NCT02017678) Phase 2 Study of JX-594 in Patients With Peritoneal Carcinomatosis of Ovarian Cancer Origin. U.S. National Institutes of Health.
Ref 11 ClinicalTrials.gov (NCT01749306) A Study of the Efficacy and Safety of ABH001 in the Treatment of Patients With Epidermolysis Bullosa Who Have Wounds That Are Not Healing. U.S. National Institutes ofHealth.
Ref 12 ClinicalTrials.gov (NCT00034333) Safety and Efficacy of Doxorubicin Adsorbed to Magnetic Beads Vs. IV Doxorubicin in Treating Liver Cancer. U.S. National Institutes of Health.
Ref 13 ClinicalTrials.gov (NCT00730158) A Phase II Multicenter, Randomized, Placebo Controlled, Double Blinded Clinical Study of KD018 as a Modulator of Irinotecan Chemotherapy in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
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 800026037)
Ref 15 PRODUCTS: BrachySil. Psivida corp
Ref 16 ClinicalTrials.gov (NCT01232452) A Study in Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 17 ClinicalTrials.gov (NCT00819650) A Trial of Licartin for Preventing Tumor Recurrence After Liver Resection. U.S. National Institutes of Health.
Ref 18 ClinicalTrials.gov (NCT00421213) Phase II Study of ZIO-101 in Advanced Blood and Bone Marrow Cancers. U.S. National Institutes of Health.
Ref 19 ClinicalTrials.gov (NCT01307891) Abraxane With or Without Tigatuzumab in Patients With Metastatic, Triple Negative Breast Cancer. U.S. National Institutes of Health.
Ref 20 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021589)
Ref 21 ClinicalTrials.gov (NCT02293850) Phase I/II Study to Evaluate the Safety and Efficacy of Telomelysin (OBP-301) in Patients With Hepatocellular Carcinoma. U.S. National Institutes of Health.
Ref 22 Clinical pipeline report, company report or official report of Metabasis Therapeutics (2006).
Ref 23 ClinicalTrials.gov (NCT00149396) Safety and Efficacy of a Genetically Engineered Herpes Simplex Virus NV1020 to Treat Colorectal Cancer Metastatic to Liver. U.S. National Institutes of Health.
Ref 24 ClinicalTrials.gov (NCT01882946) Safety and Efficacy Study of DCVax-Direct in Solid Tumors. U.S. National Institutes of Health.
Ref 25 ClinicalTrials.gov (NCT04374877) Study of SRF388 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 26 ClinicalTrials.gov (NCT03965546) Clinical Study of ET 140202 -T Cell Combined With TAE or Sorafenib in the Treatment of Advanced Liver Cancer. U.S.National Institutes of Health.
Ref 27 ClinicalTrials.gov (NCT03132792) A Phase I Open Label Clinical Trial Evaluating the Safety and Anti-Tumor Activity of Autologous T Cells Expressing Enhanced TCRs Specific for Alpha Fetoprotein (AFP????T) in HLA-A2 Positive Subjects With Advanced Hepatocellular Carcinoma (HCC) or Other AFP Expressing Tumor Types. U.S.National Institutes of Health.
Ref 28 ClinicalTrials.gov (NCT02191761) Safety and Pharmacokinetics of SM04755 in Subjects With Advanced Colorectal, Gastric, Hepatic, or Pancreatic Cancer. U.S. National Institutes of Health.
Ref 29 Clinical pipeline report, company report or official report of Progen.
Ref 30 ClinicalTrials.gov (NCT00327652) Study of Safety and Tolerability of Intravenous CRS-100 in Adults With Carcinoma and Liver Metastases. U.S. National Institutes of Health.
Ref 31 ClinicalTrials.gov (NCT03349255) Clinical Study of ET1402L1-CAR T Cells in AFP Expressing Hepatocellular Carcinoma
Ref 32 ClinicalTrials.gov (NCT02541370) Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART133
Ref 33 ClinicalTrials.gov (NCT01829971) A Multicenter Phase I Study of MRX34, MicroRNA miR-RX34 Liposomal Injection. U.S. National Institutes of Health.
Ref 34 Clinical pipeline report, company report or official report of Alnylam Pharmaceuticals, Inc (2011).
Ref 35 ClinicalTrials.gov (NCT02729493) Study Evaluating the Efficacy and Safety With CAR-T for Liver Cancer
Ref 36 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003116)
Ref 37 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015394)
Ref 38 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009854)
Ref 39 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008092)
Ref 40 Circadian rhythm as a therapeutic target. Nat Rev Drug Discov. 2021 Apr;20(4):287-307.
Ref 41 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018427)
Ref 42 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020214)
Ref 43 Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells. J Nutr. 2007 Nov;137(11):2366-70.
Ref 44 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.