Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05055
[1]
Non-coding RNA LINRIS IGF2BP2  lncRNA       miRNA   circRNA Direct Enhancement m6A modification MYC MYC IGF2BP2 : m6A sites
m6A Modification:
m6A Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
m6A Target Myc proto-oncogene protein (MYC)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Long intergenic non-protein coding RNA 920 (LINC00920) LncRNA View Details
Regulated Target Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) View Details
Crosstalk Relationship ncRNA  →  m6A Enhancement
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary LncRNA LINC00920 stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer.LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-Myc proto-oncogene protein (MYC) axis promotes the progression of CRC and is a promising therapeutic target.
Responsed Disease Colorectal cancer ICD-11: 2B91
Pathway Response Ubiquitin mediated proteolysis hsa04120
Glycolysis / Gluconeogenesis hsa00010
Cell Process Autophagy-lysosome pathway
Ubiquitination
Glycolysis
In-vivo Model For the orthotopic models, 2 × 106 cells with negative control (NC, sh-NC), sh-1 or sh-2 in 0.5 mL of PBS were subcutaneously injected into the dorsal flank of 2 mice respectively. After the tumors grew up to 1 cm3, they were resected and equally divided into small pieces. Then 15 mice were separated into 3 groups (sh-NC, sh-1 and sh-2), of which the tumor pieces were tied to the base of the ceca.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Myc proto-oncogene protein (MYC) 3 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name AVI-5126 Phase 2 [2]
Synonyms
Resten-CP; NeuGene (CABG), AVI
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 Compound Name Resten-NG Phase 2 [3]
Synonyms
Resten-NG (TN)
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 Compound Name TWS-119 Investigative [4]
Synonyms
TWS119; 601514-19-6; 3-[[6-(3-Aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenol; TWS 119; GSK inhibitor XII; GSK-3beta Inhibitor XII, TWS119; Neurogenesis Inducer, TWS119; CHEMBL405759; 3-(6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenol; 3-((6-(3-AMINOPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)OXY)PHENOL; 3-{[6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy}phenol; Phenol, 3-[[6-(3-aminophenyl)-1H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]-; K00245; MLS006011018; GTPL5980; SCHEMBL5559045; GSK-3BETA INHIB
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2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [5]
Synonyms
INCMGA0012; Retifanlimab
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 Compound Name Aflibercept Approved [6]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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External Link
 Compound Name Regorafenib Approved [7]
Synonyms
755037-03-7; BAY 73-4506; Regorafenibum; Stivarga; 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide; BAY73-4506; Regorafenib (BAY 73-4506); UNII-24T2A1DOYB; 4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; BAY-73-4506; 24T2A1DOYB; CHEMBL1946170; CHEBI:68647; Stivarga (TN); BAY73-4506 hydrochloride; Regorafenib [USAN:INN]
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 Compound Name Bevacizumab Approved [8]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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 Compound Name SYM-004 Phase 3 [8]
Synonyms
Chimeric IgG1 antibody 1024 (cancer), Symphogen; Chimeric IgG1 antibody 992 (cancer), Symphogen; Chimeric IgG1 antibodies992 + 1024 (cancer), Symphogen
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 Compound Name Bevacizumab + Erlotinib Phase 3 [9]
External Link
 Compound Name CPI-613 Phase 3 [8]
Synonyms
95809-78-2; 6,8-bis(benzylthio)octanoic acid; CPI 613; MLS006010202; SCHEMBL1062218; 6,8-Bis(benzylsulfanyl)octanoic acid; Octanoic acid, 6,8-bis((phenylmethyl)thio)-; Octanoic acid, 6,8-bis[(phenylMethyl)thio]-; 6,8-Bis[(phenylmethyl)thio]octanoic acid; CPI613; CHEMBL3186849; QCR-193; AOB1058; MolPort-023-219-128; HMS3656L06; C22H28O2S2; BCP04663; EX-A2043; s2776; AKOS025142095; BCP9000552; DB12109; RL06062; CS-0961; NCGC00344764-01; SMR004701300; AS-16613; BC261916; AK174899; HY-15453; BCP0726000030; KB-293127; AB0035874
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 Compound Name Bevacizumab Approved [6]
External Link
 Compound Name AlloStim Phase 2/3 [10]
Synonyms
AlloStim (TN)
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 Compound Name Sibrotuzumab Phase 2 [11]
External Link
 Compound Name CV301 Phase 2 [12]
External Link
 Compound Name Efatutazone Phase 2 [13]
Synonyms
Inolitazone; 223132-37-4; 5-[[4-[[6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-yl]methoxy]phenyl]methyl]-2,4-Thiazolidinedione; Efatutazone [INN]; RS5444; CS-7017; SCHEMBL3246054; CHEMBL3545280; JCYNMRJCUYVDBC-UHFFFAOYSA-N; Efatutazone;CS-7017;RS5444; BCP07478; AKOS030526729; DB11894; CS-0778; KB-77905; DA-07988; HY-14792; QC-10456; 4CA-1384; FT-0737589; 5-[4-[6-(4-amino-3 ,5-dimethylphenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione
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 Compound Name LOR-2040 Phase 2 [14]
External Link
 Compound Name RG7221 Phase 2 [15]
External Link
 Compound Name PEG-SN38 Phase 2 [16]
Synonyms
EZN-2208
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 Compound Name MEGF0444A Phase 2 [17]
External Link
 Compound Name Encapsulated cell therapy Phase 1/2 [18]
External Link
 Compound Name AB928 Phase 1/2 [19]
External Link
 Compound Name MGD007 Phase 1 [15]
External Link
 Compound Name BNC-101 Phase 1 [20]
External Link
 Compound Name Navicixizumab Phase 1 [8]
External Link
 Compound Name RG7160 Discontinued in Phase 2 [21]
External Link
 Compound Name Nimesulide Terminated [22]
Synonyms
51803-78-2; N-(4-Nitro-2-phenoxyphenyl)methanesulfonamide; Mesulid; Flogovital; Sulidene; Nimed; R-805; 4-NITRO-2-PHENOXYMETHANESULFONANILIDE; Nisulid; Nimesulidum [INN-Latin]; Nimesulida [INN-Spanish]; R 805; UNII-V4TKW1454M; 4-Nitro-2-phenoxy-methanesulfonanilide; 4'-Nitro-2'-phenoxymethanesulfonanilide; Methanesulfonamide, N-(4-nitro-2-phenoxyphenyl)-; EINECS 257-431-4; 4'-Nitro-2'-phenoxymethansulfonanilid; BRN 2421175; CHEMBL56367; MLS000069680; V4TKW1454M; Methanesulfonanilide, 4'-nitro-2'-phenoxy-; CHEBI:44445; Dulanermin
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 Compound Name Saracatinib Phase 2 [23]
External Link
 Compound Name G3139 + Irinotecan Investigative [24]
External Link
References
Ref 1 LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer. Mol Cancer. 2019 Dec 2;18(1):174. doi: 10.1186/s12943-019-1105-0.
Ref 2 Efficacy of a phosphorodiamidate morpholino oligomer antisense compound in the inhibition of corneal transplant rejection in a rat cornea transplant model. J Ocul Pharmacol Ther. 2012 Apr;28(2):194-201. doi: 10.1089/jop.2011.0135. Epub 2011 Dec 7.
Ref 3 Local delivery of c-myc neutrally charged antisense oligonucleotides with transport catheter inhibits myointimal hyperplasia and positively affects vascular remodeling in the rabbit balloon injury model. Catheter Cardiovasc Interv. 2001 Oct;54(2):247-56. doi: 10.1002/ccd.1277.
Ref 4 TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751.
Ref 5 Development of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signaling Pathway.J Med Chem. 2019 Feb 28;62(4):1715-1730.
Ref 6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 7 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: 5891).
Ref 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 9 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 11 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 12 ClinicalTrials.gov (NCT03547999) A Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Metastatic CRC. U.S. National Institutes of Health.
Ref 13 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 14 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 15 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 16 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 17 ClinicalTrials.gov (NCT00909740) A Study of the Safety and Pharmacokinetics of MEGF0444A Administered to Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 18 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 19 ClinicalTrials.gov (NCT04660812) An Open Label Study Evaluating the Efficacy and Safety of AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 20 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 21 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029052)
Ref 22 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 23 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 24 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.