m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03529
 [1], [2]
Histone modification H3K4me3 WDR5 METTL3 Direct Enhancement m6A modification NEK2 NEK2 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Serine/threonine-protein kinase Nek2 (NEK2)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator WD repeat-containing protein 5 (WDR5) WRITER View Details
Regulated Target Histone H3 lysine 4 trimethylation (H3K4me3) View Details
Downstream Gene METTL3 View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
Crosstalk Summary The transcription factor ETS1 recruited P300 and WDR5 which separately mediated H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. The METTL3-Serine/threonine-protein kinase Nek2 (NEK2) axis promoted CC progression by activating the Wnt/beta-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy.
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
In-vitro Model
 HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Serine/threonine-protein kinase Nek2 (NEK2) 3 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PMID21627121C2 Investigative [3]
Synonyms
GTPL8149; BDBM50418829
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MOA Inhibitor
Activity IC50 < 6 nM
External Link
CID: 16662746
TTD: D0C3KE
 Compound Name PMID20936789C31 Investigative [4]
Synonyms
GTPL8180; BDBM50330575
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MOA Inhibitor
Activity IC50 = 230 nM
External Link
CID: 49837564
TTD: D0K0UJ
 Compound Name GSK579289A Investigative [5]
Synonyms
compound 25 [PMID 19237286]; GSK-579289A
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MOA Inhibitor
Activity IC50 = 21 nM
External Link
CID: 16051023
TTD: D0X1RH
WD repeat-containing protein 5 (WDR5) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name OICR-9429 Investigative [6]
Synonyms
1801787-56-3; OICR9429; CHEMBL3798846; N-(4-(4-Methylpiperazin-1-Yl)-3'-(Morpholinomethyl)-[1,1'-Biphenyl]-3-Yl)-6-Oxo-4-(Trifluoromethyl)-1,6-Dihydropyridine-3-Carboxamide; N-[2-(4-methylpiperazin-1-yl)-5-[3-(morpholin-4-ylmethyl)phenyl]phenyl]-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide; GTPL8231; OICR 9429; MolPort-039-101-294; EX-A2417; BCP18185; BDBM50164794; s7833; AKOS025147341; ZINC231558892; SB19642; CS-5776; NCGC00371263-02; AK468854; HY-16993; J3.618.049H
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MOA Antagonist
External Link
CID: 91623360
TTD: D0XI3W
References
Ref 1 METTL3 potentiates progression of cervical cancer by suppressing ER stress via regulating m6A modification of TXNDC5 mRNA. Oncogene. 2022 Sep;41(39):4420-4432. doi: 10.1038/s41388-022-02435-2. Epub 2022 Aug 20.
Ref 2 METTL3 facilitates the progression of cervical cancer by m6A modification-mediated up-regulation of NEK2. Sci Rep. 2024 Oct 18;14(1):24469. doi: 10.1038/s41598-024-73601-7.
Ref 3 Irreversible Nek2 kinase inhibitors with cellular activity. J Med Chem. 2011 Jun 23;54(12):4133-46.
Ref 4 Aminopyrazine inhibitors binding to an unusual inactive conformation of the mitotic kinase Nek2: SAR and structural characterization. J Med Chem. 2010 Nov 11;53(21):7682-98.
Ref 5 Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1694-7. doi: 10.1016/j.bmcl.2009.01.094. Epub 2009 Jan 31.
Ref 6 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. (Target id: 2831).