m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03522
 [1], [2]
Histone modification H3K4me3 WDR5 METTL3 Direct Enhancement m6A modification CCND1 CCND1 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target G1/S-specific cyclin-D1 (CCND1)
 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. METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through G1/S-specific cyclin-D1 (CCND1) targeting.
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
In-vitro Model
 SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
In-vivo Model Mice were divided into two groups (n = 4/group) randomly. 3× 106 cells suspended in 200 uL PBS were administered via subcutaneous injection over the right flank region of nude mice. After the development of palpable tumors (average volume, 50 mm3), intratumoral injection of synthetic miR-193b, or negative control complexed with siPORT Amine transfection reagent (Ambion, USA) was given 6 times at a 4-day interval.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
G1/S-specific cyclin-D1 (CCND1) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name ABT-263 Phase 3 [3]
Synonyms
Navitoclax; ABT 263; S1001_Selleck; ABT263, Navitoclax; 4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-({(1R)-3-morpholin-4-yl-1-[(phenylsulfanyl)methyl]propyl}amino)-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide
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MOA Inhibitor
External Link
CID: 24978538
TTD: D06ETI
DrugBank: DB12340
 Compound Name Briciclib Phase 1 [4]
Synonyms
865783-99-9; ON-014185; UNII-WG93X96336; WG93X96336; ON 014185; Briciclib [USAN:INN]; Briciclib (USAN/INN); SCHEMBL1634579; SCHEMBL1634581; CHEMBL1206245; MolPort-046-033-539; LXENKEWVEVKKGV-BQYQJAHWSA-N; EX-A2492; BCP17292; ZINC28965775; AKOS027439966; DB12004; CS-5589; HY-16366; KB-79924; Briciclib(ON 013105 ON 014185); ON-013105; D10614; (2-methoxy-5-{[(E)-2-(2,4,6-trimethoxyphenyl)ethenesulfonyl]methyl}phenoxy)phosphonic acid; (e)-5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenyl dihydro
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MOA Inhibitor
External Link
CID: 11248490
TTD: D0T0KT
DrugBank: DB12004
 Compound Name 7-hydroxycoumarin Investigative [5]
Synonyms
Umbelliferone; 93-35-6; 7-Hydroxy-2H-chromen-2-one; Skimmetin; Hydrangin; 7-hydroxycoumarine; 7-Oxycoumarin; Umbelliferon; Skimmetine; Hydrangine; 2H-1-Benzopyran-2-one, 7-hydroxy-; 7-Hydroxy-2H-1-benzopyran-2-one; Coumarin, 7-hydroxy-; beta-Umbelliferone; 7-hydroxychromen-2-one; 7 HC; UNII-60Z60NTL4G; 7-hydroxy-coumarin; NSC 19790; CCRIS 3591; NSC19790; EINECS 202-240-3; 7H-1-Benzopyran-7-one, 2-hydroxy-; BRN 0127683; CHEMBL51628; AI3-38054; 7-hydroxy-1-benzopyran-2-one; 7-HC; 60Z60NTL4G; CHEBI:27510
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MOA Inhibitor
External Link
CID: 5281426
TTD: D02JEZ
 Compound Name 3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione Investigative [6]
Synonyms
CHEMBL380598; SCHEMBL3148490; HVQJGNALTWNDMX-UHFFFAOYSA-N; BDBM50375058; 2-(1H-Indole-3-yl)-3-phenylmaleimide
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MOA Inhibitor
External Link
CID: 15422868
TTD: D06AOY
 Compound Name 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Investigative [6]
Synonyms
1H-Pyrrole-2,5-dione, 3,4-bis(4-methoxyphenyl)-; 108774-82-9; ACMC-20mbs9; CHEMBL381099; CTK0G2626; DTXSID90449388
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MOA Inhibitor
External Link
CID: 10946795
TTD: D00NYT
 Compound Name 3,4-diphenyl-1H-pyrrole-2,5-dione Investigative [6]
Synonyms
2,3-diphenylmaleimide; 1H-Pyrrole-2,5-dione, 3,4-diphenyl-; 31295-36-0; AC1MBL6S; SCHEMBL114611; CHEMBL201949; CTK1B9880; 3,4-diphenylpyrrole-2,5-dione; DTXSID70372903; ZINC3847556
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MOA Inhibitor
External Link
CID: 2752461
TTD: D0C3WY
 Compound Name 3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione Investigative [6]
Synonyms
CHEMBL372076; SCHEMBL3822337
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MOA Inhibitor
External Link
CID: 11572699
TTD: D0EK0G
 Compound Name 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Investigative [7]
MOA Inhibitor
External Link
CID: 9859248
TTD: D0A5RM
WD repeat-containing protein 5 (WDR5) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name OICR-9429 Investigative [8]
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 N(6)-Methyladenosine Associated Silencing of miR-193b Promotes Cervical Cancer Aggressiveness by Targeting CCND1. Front Oncol. 2021 Jun 10;11:666597. doi: 10.3389/fonc.2021.666597. eCollection 2021.
Ref 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 4 Clinical pipeline report, company report or official report of Onconova.
Ref 5 Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin. Lung Cancer. 2001 Nov;34(2):185-94. doi: 10.1016/s0169-5002(01)00263-x.
Ref 6 Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81. doi: 10.1021/jm0580297.
Ref 7 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9. doi: 10.1021/jm0605740.
Ref 8 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).