Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05268
[1], [2]
Non-coding RNA miR-136-5p YTHDF1  lncRNA       miRNA   circRNA Direct Enhancement m6A modification ARHGEF2 ARHGEF2 YTHDF1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 1 (YTHDF1) READER
m6A Target Rho guanine nucleotide exchange factor 2 (ARHGEF2)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-136-5p microRNA View Details
Regulated Target YTH domain-containing family protein 1 (YTHDF1) View Details
Crosstalk Relationship ncRNA  →  m6A Enhancement
Crosstalk Mechanism ncRNAs directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary hsa-miR-136-5p targeted YTHDF1 to restrain CRC progression and chemoresistance.YTHDF1 promotes cell growth in CRC cell lines and primary organoids and lung and liver metastasis in vivo. YTHDF1 binds to m6A sites of Rho guanine nucleotide exchange factor 2 (ARHGEF2) messenger RNA, resulting in enhanced translation of ARHGEF2.
Responsed Disease Colorectal cancer ICD-11: 2B91
In-vitro Model
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
RKO Colon carcinoma Homo sapiens CVCL_0504
SW1116 Colon adenocarcinoma Homo sapiens CVCL_0544
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
LoVo Colon adenocarcinoma Homo sapiens CVCL_0399
LS180 Colon adenocarcinoma Homo sapiens CVCL_0397
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 [3]
Synonyms
INCMGA0012; Retifanlimab
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 Compound Name Aflibercept Approved [4]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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 Compound Name Regorafenib Approved [5]
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 [6]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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 Compound Name SYM-004 Phase 3 [6]
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 [7]
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 Compound Name CPI-613 Phase 3 [6]
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 [4]
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 Compound Name AlloStim Phase 2/3 [8]
Synonyms
AlloStim (TN)
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 Compound Name Sibrotuzumab Phase 2 [9]
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 Compound Name CV301 Phase 2 [10]
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 Compound Name Efatutazone Phase 2 [11]
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 [12]
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 Compound Name RG7221 Phase 2 [13]
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 Compound Name PEG-SN38 Phase 2 [14]
Synonyms
EZN-2208
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 Compound Name MEGF0444A Phase 2 [15]
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 Compound Name Encapsulated cell therapy Phase 1/2 [16]
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 Compound Name AB928 Phase 1/2 [17]
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 Compound Name MGD007 Phase 1 [13]
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 Compound Name BNC-101 Phase 1 [18]
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 Compound Name Navicixizumab Phase 1 [6]
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 Compound Name RG7160 Discontinued in Phase 2 [19]
External Link
 Compound Name Nimesulide Terminated [20]
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 [21]
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 Compound Name G3139 + Irinotecan Investigative [22]
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References
Ref 1 Statement of Retraction: Circular RNA protein tyrosine kinase 2 (circPTK2) promotes colorectal cancer proliferation, migration, invasion and chemoresistance. Bioengineered. 2023 Dec;14(1):2269352. doi: 10.1080/21655979.2023.2269352. Epub 2023 Oct 18.
Ref 2 N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer. Gastroenterology. 2022 Apr;162(4):1183-1196. doi: 10.1053/j.gastro.2021.12.269. Epub 2021 Dec 28.
Ref 3 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 4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 5 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).
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Ref 9 ClinicalTrials.gov (NCT02198274) Intravenous BIBH 1 in Patients With Metastatic Colorectal Cancer. U.S. National Institutes of Health.
Ref 10 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 11 ClinicalTrials.gov (NCT02152137) Efatutazone With Paclitaxel Versus Paclitaxel Alone in Treating Patients With Advanced Anaplastic Thyroid Cancer. U.S. National Institutes of Health.
Ref 12 ClinicalTrials.gov (NCT00087165) GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer. U.S. National Institutes of Health.
Ref 13 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 14 ClinicalTrials.gov (NCT01036113) A Phase 2 Study of EZN-2208 in Patients With Metastatic Breast Cancer. U.S. National Institutes of Health.
Ref 15 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 16 VC-01's Path to the Clinic. Viacyte. 2015.
Ref 17 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 18 ClinicalTrials.gov (NCT02726334) A Phase I, Dose Escalation Study of BNC101 in Patients With Metastatic Colorectal Cancer.. U.S. National Institutes of Health.
Ref 19 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 20 Clinical pipeline report, company report or official report of Genentech (2011).
Ref 21 Phase II Study of Saracatinib (AZD0530) in Patients With Previously Treated Metastatic Colorectal Cancer. Invest New Drugs. 2015 Aug;33(4):977-84.
Ref 22 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.