Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05296
[1]
Non-coding RNA RP11 HNRNPA2B1  lncRNA       miRNA   circRNA Direct Enhancement m6A modification FBXO45 FBXO45 hnRNPA2B1 : m6A sites
m6A Modification:
m6A Regulator Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) READER
m6A Target F-box/SPRY domain-containing protein 1 (FBXO45)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator RP11-138 J23.1 (RP11) LncRNA View Details
Regulated Target Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) View Details
Crosstalk Relationship ncRNA  →  m6A Enhancement
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary the RP11/HNRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and F-box/SPRY domain-containing protein 1 (FBXO45), and subsequently prevented the proteasomal degradation of Zeb1.m6A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1
Responsed Disease Colorectal cancer ICD-11: 2B91
Pathway Response Proteasome hsa03050
Cell Process Proteasomal degradation
In-vivo Model To evaluate the potential roles of RP11 in the growth of CRC, ten female BALB/c nude mice randomly divided into two groups. HCT-15 RP11 stable overexpression or control cells (2 × 106 per mouse) diluted in 100 μl normal medium + 100 μl Matrigel (BD Biosciences) were subcutaneously injected into immunodeficient mice to investigate tumour growth.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2B91: Colorectal cancer 25 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Retifanlimab Approved [2]
Synonyms
INCMGA0012; Retifanlimab
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 Compound Name Aflibercept Approved [3]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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 Compound Name Regorafenib Approved [4]
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 [5]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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 Compound Name SYM-004 Phase 3 [5]
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 [6]
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 Compound Name CPI-613 Phase 3 [5]
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 [3]
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 Compound Name AlloStim Phase 2/3 [7]
Synonyms
AlloStim (TN)
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 Compound Name Sibrotuzumab Phase 2 [8]
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 Compound Name CV301 Phase 2 [9]
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 Compound Name Efatutazone Phase 2 [10]
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 [11]
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 Compound Name RG7221 Phase 2 [12]
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 Compound Name PEG-SN38 Phase 2 [13]
Synonyms
EZN-2208
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 Compound Name MEGF0444A Phase 2 [14]
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 Compound Name Encapsulated cell therapy Phase 1/2 [15]
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 Compound Name AB928 Phase 1/2 [16]
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 Compound Name MGD007 Phase 1 [12]
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 Compound Name BNC-101 Phase 1 [17]
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 Compound Name Navicixizumab Phase 1 [5]
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 Compound Name RG7160 Discontinued in Phase 2 [18]
External Link
 Compound Name Nimesulide Terminated [19]
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 [20]
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 Compound Name G3139 + Irinotecan Investigative [21]
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References
Ref 1 m(6)A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1. Mol Cancer. 2019 Apr 13;18(1):87. doi: 10.1186/s12943-019-1014-2.
Ref 2 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 3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 4 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 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 8 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 9 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 10 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 11 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 12 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 13 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 14 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 15 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 16 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 17 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 18 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 19 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 20 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 21 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.