m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05270
 [1], [2]
Non-coding RNA miR-136-5p YTHDF1  lncRNA       miRNA   circRNA Direct Enhancement m6A modification GID8 GID8 YTHDF1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
m6A Target Glucose-induced degradation protein 8 homolog (GID8)
 Targert Gene 
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.Glucose-induced degradation protein 8 homolog (GID8)/Twa1 as a crucial downstream target of YTHDF1. YTHDF1 manipulates GID8 translation efficiency in an m6A-dependent manner, and high expression of GID8 is associated with more aggressive tumor progression and poor overall survival.GID8 is intimately associated with glutamine metabolic demands by maintaining active glutamine uptake and metabolism through the regulation of excitatory amino acid transporter 1 (SLC1A3) and glutaminase (GLS), thereby facilitating the malignant progression of CRC. Inhibition of GID8 attenuated CRC proliferation and metastasis both in vitro and in vivo.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
In-vitro Model
 SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
NCM460 Normal Homo sapiens CVCL_0460
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Sh-GID8 stable cells (2 × 106) were inoculated subcutaneously into the left axilla of athymic nude mice (n = 5 mice/group). Every three days, the tumor's size was measured with a digital caliper, and its volume was computed using the following formula: tumor volume (mm3) = length × width × width × 0.52. When the subcutaneous tumor reached approximately 50-100 mm3, glutamine (75 mg/kg) [13] or PBS was injected intratumorally every day. Tumors were collected for TUNEL staining or other analysis when tumor volumes reached the humane endpoint. For the metastasis model, the constructed HCT116 cells (2 × 106) with stable YTHDF1 or GID8 knockdown were injected into nude mice through the tail vein (n = 4 or n = 5 mice/group). Two months later, all the mice were sacrificed to observe tumor metastasis in the lungs.
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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TTD: D0PG5O
 Compound Name Aflibercept Approved [4]
Synonyms
Ziv-Aflibercept; Zaltrap (TN); VEGF Trap; VEGF Trap-Eye
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TTD: D0C9ET
 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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CID: 11167602
TTD: D09GDD
DrugBank: DB08896
 Compound Name Bevacizumab Approved [6]
Synonyms
Bevacizumab (ophthalmic slow-release tissue tablet)
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TTD: D04KBL
 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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TTD: D0CR8H
 Compound Name Bevacizumab + Erlotinib Phase 3 [7]
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TTD: D09BKY
 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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CID: 24770514
TTD: D07NVI
DrugBank: DB12109
 Compound Name Bevacizumab Approved [4]
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TTD: D0FX3U
 Compound Name AlloStim Phase 2/3 [8]
Synonyms
AlloStim (TN)
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TTD: D0B3CC
 Compound Name Sibrotuzumab Phase 2 [9]
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TTD: DVX3H0
 Compound Name CV301 Phase 2 [10]
External Link
TTD: D9LT5G
 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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CID: 9832447
TTD: D0Y8NZ
DrugBank: DB11894
 Compound Name LOR-2040 Phase 2 [12]
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TTD: D0I7NG
 Compound Name RG7221 Phase 2 [13]
External Link
TTD: D06FTM
 Compound Name PEG-SN38 Phase 2 [14]
Synonyms
EZN-2208
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CID: 59443782
TTD: D05UFP
 Compound Name MEGF0444A Phase 2 [15]
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TTD: D01LES
 Compound Name Encapsulated cell therapy Phase 1/2 [16]
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TTD: D0XY8C
 Compound Name AB928 Phase 1/2 [17]
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CID: 135242184
TTD: D04UBI
 Compound Name MGD007 Phase 1 [13]
External Link
TTD: D00PEN
 Compound Name BNC-101 Phase 1 [18]
External Link
TTD: DD6AZ5
 Compound Name Navicixizumab Phase 1 [6]
External Link
TTD: D00IVN
 Compound Name RG7160 Discontinued in Phase 2 [19]
External Link
TTD: D0E2CQ
 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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CID: 4495
TTD: D0C0JT
DrugBank: DB04743
 Compound Name Saracatinib Phase 2 [21]
External Link
CID: 10302451
TTD: D05YTN
DrugBank: DB11805
 Compound Name G3139 + Irinotecan Investigative [22]
External Link
CID: 91865905
TTD: D05IAN
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 YTHDF1 regulates GID8-mediated glutamine metabolism to promote colorectal cancer progression in m6A-dependent manner. Cancer Lett. 2024 Oct 1;601:217186. doi: 10.1016/j.canlet.2024.217186. Epub 2024 Aug 14.
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).
Ref 6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 7 ClinicalTrials.gov (NCT00130728) A Study to Evaluate the Efficacy of Bevacizumab in Combination With Tarceva for Advanced Non-Small Cell Lung Cancer
Ref 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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.