m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT02196
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[1], [2] | |||
DNA methylation
DNMT3A
PTPN13
Indirect
Inhibition
m6A modification
MARCKSL1
MARCKSL1
IGF2BP1
: m6A sites
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| m6A Modification: | |||||
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| m6A Regulator | Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) | READER | |||
| m6A Target | MARCKS-related protein (MARCKSL1) | ||||
| Epigenetic Regulation that have Cross-talk with This m6A Modification: | |||||
| Epigenetic Regulation Type | DNA methylation (DNAMeth) | ||||
| Epigenetic Regulator | Cysteine methyltransferase DNMT3A (DNMT3A) | WRITER | View Details | ||
| Regulated Target | Protein tyrosine phosphatase non-receptor type 13 (PTPN13) | View Details | |||
| Crosstalk Relationship | DNA methylation → m6A | Inhibition | |||
| Crosstalk Mechanism | DNA methylation indirectly regulates m6A modification through downstream signaling pathways | ||||
| Crosstalk Summary | We identified Protein tyrosine phosphatase non-receptor type 13 (PTPN13) expression by upregulating the expression of DNMT3A and IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Four representative high confidence targets, including MYC, FSCN1, TK1, and MARCKS-related protein (MARCKSL1), exhibit strong binding with IGF2BPs around their m6A motifs in control cells. Knocking down of each individual IGF2BPs in Hela (cervical cancer) and HepG2 (liver cancer) cells significantly repressed MYC expression. | ||||
| Responsed Disease | Liver cancer | ICD-11: 2C12 | |||
| Cell Process | RNA decay | ||||
In-vitro Model |
Hep-G2/2.2.15 | Hepatoblastoma | Homo sapiens | CVCL_L855 | |
| Huh-7 | Adult hepatocellular carcinoma | Homo sapiens | CVCL_0336 | ||
| L-02 | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | ||
| Hep-G2 | Hepatoblastoma | Homo sapiens | CVCL_0027 | ||
| SK-HEP-1 | Liver and intrahepatic bile duct epithelial neoplasm | Homo sapiens | CVCL_0525 | ||
| MHCC97-L | Adult hepatocellular carcinoma | Homo sapiens | CVCL_4973 | ||
| LM3 | Malignant neoplasms | Mus musculus | CVCL_D269 | ||
| MHCC97-H | Adult hepatocellular carcinoma | Homo sapiens | CVCL_4972 | ||
| L-02 | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | ||
| SMMC-7721 | Endocervical adenocarcinoma | Homo sapiens | CVCL_0534 | ||
| PLC/PRF/5 | Adult hepatocellular carcinoma | Homo sapiens | CVCL_0485 | ||
| Hep 3B2.1-7 | Childhood hepatocellular carcinoma | Homo sapiens | CVCL_0326 | ||
| In-vivo Model | A total of 3 x 106 cells were suspended and mixed with Matrigel (BD Biosciences, Bedford, MA, USA) at a 1:3 volume ratio in 100 μ L of serum-free DMEM and injected subcutaneously into mice. Tumor volumes were measured every 3 days using a caliper and calculated using the standard formula V = shortest diameter2× longest diameter/2. The mice were euthanized when animals exhibited either 30 days after subcutaneous injection or large tumors (volume > 1500 mm3) or obvious signs of discomfort. The tumor was removed, photographed and weighed before being fixed in 10% buffered formalin and analyzed by hematoxylin and eosin (H&E) staining and IHC. | ||||
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
| Cysteine methyltransferase DNMT3A (DNMT3A) | 8 Compound(s) Regulating the Target | Click to Show/Hide the Full List | ||
| PMID27376512-Compound-Figure3CN | Patented | [3] | ||
| MOA | Inhibitor | |||
| Activity | EC50 = 1100 nM | |||
| External Link | ||||
| PMID27376512-Compound-Figure3CG | Patented | [3] | ||
| MOA | Inhibitor | |||
| Activity | EC50 = 2400 nM | |||
| External Link | ||||
| PMID27376512-Compound-Figure3CM | Patented | [3] | ||
| MOA | Inhibitor | |||
| Activity | EC50 = 1100 nM | |||
| External Link | ||||
| PMID27376512-Compound-Figure2aExample1 | Patented | [3] | ||
| MOA | Inhibitor | |||
| Activity | IC50 = 3000 nM | |||
| External Link | ||||
| PMID27376512-Compound-MTC-424 | Patented | [3] | ||
| MOA | Inhibitor | |||
| Activity | IC50 = 1940 nM | |||
| External Link | ||||
| PMID27376512-Compound-MTC-427 | Patented | [3] | ||
| MOA | Inhibitor | |||
| Activity | IC50 = 295 nM | |||
| External Link | ||||
| PMID27376512-Compound-MTC-422 | Patented | [3] | ||
| MOA | Inhibitor | |||
| Activity | IC50 = 1430 nM | |||
| External Link | ||||
| PMID27376512-Compound-MTC-423 | Patented | [3] | ||
| MOA | Inhibitor | |||
| Activity | IC50 = 363 nM | |||
| External Link | ||||
| Protein tyrosine phosphatase non-receptor type 13 (PTPN13) | 2 Compound(s) Regulating the Target | Click to Show/Hide the Full List | ||
| US9217012, 10 | Patented | [4] | ||
| Synonyms |
SCHEMBL19222783; CHEMBL3969776; BDBM199180
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| MOA | Inhibitor | |||
| External Link | ||||
| ISIS 18473 | Investigative | [5] | ||
| External Link | ||||
| 2C12: Liver cancer | 49 Compound(s) Regulating the Disease | Click to Show/Hide the Full List | ||
| 90Y-loaded resin microspheres | Approved | [6] | ||
| External Link | ||||
| Thymalfasin | Phase 2 | [7] | ||
| 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
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| Ferumoxides | Approved | [8] | ||
| 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
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| External Link | ||||
| DTI-015 | Approved | [9] | ||
| 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
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| External Link | ||||
| Nofazinlimab | Phase 3 | [10] | ||
| Synonyms |
CS1003; EQ176
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| External Link | ||||
| PV-10 | Phase 3 | [11] | ||
| 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
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| External Link | ||||
| Brivanib | Phase 3 | [12] | ||
| 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
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| External Link | ||||
| JX-594 | Phase 3 | [13] | ||
| Synonyms |
Pexastimogene devacirepvec
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| External Link | ||||
| ABH001 | Phase 3 | [14] | ||
| External Link | ||||
| MTC-DOX | Phase 2/3 | [15] | ||
| Synonyms |
MTC-doxorubicin
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| External Link | ||||
| KD018 | Phase 2 | [16] | ||
| External Link | ||||
| Doxorubicin-eluting beads | Phase 2 | [17] | ||
| Synonyms |
DC Bead (TN)
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| 32-P BioSilicon | Phase 2 | [18] | ||
| Synonyms |
BrachySil
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| Cixutumumab | Phase 2 | [19] | ||
| Synonyms |
LY3012217
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| [131I]-Metuximab | Phase 2 | [20] | ||
| External Link | ||||
| Darinaparsin | Phase 2 | [21] | ||
| Synonyms |
ZIO-101
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| Tigatuzumab | Phase 2 | [22] | ||
| External Link | ||||
| CMC-001 | Phase 2 | [23] | ||
| Synonyms |
Manganese-based MRI contrast agent (liver tumor imaging), CMC Contrast
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| External Link | ||||
| OBP-301 | Phase 1/2 | [24] | ||
| External Link | ||||
| MBO7133 | Phase 1/2 | [25] | ||
| External Link | ||||
| INCB62079 | Phase 1/2 | [11] | ||
| External Link | ||||
| NV-1020 | Phase 1/2 | [26] | ||
| External Link | ||||
| DCVax-Liver | Phase 1/2 | [27] | ||
| Synonyms |
Dendritic cell-based immunotherapy (liver cancer), Northwest Biotherapeutics
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| SRF388 | Phase 1 | [28] | ||
| External Link | ||||
| ET140202 | Phase 1 | [29] | ||
| External Link | ||||
| ADP-A2AFP | Phase 1 | [30] | ||
| External Link | ||||
| SM04755 | Phase 1 | [31] | ||
| External Link | ||||
| Anti-CEA CAR-T therapy | Phase 1 | [11] | ||
| External Link | ||||
| PI-166 | Phase 1 | [32] | ||
| External Link | ||||
| CRS-100 | Phase 1 | [33] | ||
| External Link | ||||
| Autologous ET1402L1-CART cells | Phase 1 | [34] | ||
| External Link | ||||
| Anti-CD133-CAR vector-transduced T cells | Phase 1 | [35] | ||
| External Link | ||||
| MRX34 | Phase 1 | [36] | ||
| External Link | ||||
| ALN-VSP | Phase 1 | [37] | ||
| External Link | ||||
| EPCAM-targeted CAR-T cells | Clinical trial | [38] | ||
| External Link | ||||
| ADI | Discontinued in Phase 3 | [39] | ||
| Synonyms |
Arginine deiminase
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| GN-1140 | Discontinued in Phase 2 | [40] | ||
| External Link | ||||
| OGT-719 | Discontinued in Phase 2 | [41] | ||
| Synonyms |
OGS-719
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| AFP-Scan | Discontinued in Phase 2 | [42] | ||
| External Link | ||||
| SR1078 | Preclinical | [43] | ||
| 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
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| Occlusin | Preclinical | [44] | ||
| Synonyms |
Occlusin 50 Injection; Occlusin 500 injection
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| HRC-201 | Terminated | [45] | ||
| Synonyms |
Hemoglobin-imaging conjugate (HepSelect), Hemosol
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| 1,2,3,4,5,6-hexabromocyclohexane | Investigative | [46] | ||
| 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
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| STP-322 | Investigative | [47] | ||
| Synonyms |
Multi-targeted siRNA therapeutic cocktail (nanoparticle, liver tumor), Sirnaomics
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| AMB-8LK | Investigative | [47] | ||
| 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
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| MiR-34a mimics | Investigative | [47] | ||
| Synonyms |
MiR-34a mimics (liver cancer)
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| P53 fusion protein | Investigative | [47] | ||
| Synonyms |
P53 fusion protein (pancreatic/liver cancer)
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| OP-05 | Investigative | [47] | ||
| Synonyms |
OP-05 program (prodrug, liver tumor); OP-05 program (prodrug, liver tumor), Onco-Pharmakon
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| GR-DD1 | Investigative | [47] | ||
| Synonyms |
Cytotoxin (hepatic metastasis), ERYtech
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References
: m6A sites