Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00588
[1], [2], [3]
m6A modification hsa-miR-193b hsa-miR-193b METTL3 Methylation : m6A sites Indirect Enhancement RNA modification CCND1 CCND1 METTL1 Methylation : modification sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target hsa-miR-193b
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> N7-methylguanosine (m7G)
Epigenetic Regulator Methyltransferase-like protein 1 (METTL1) WRITER View Details
Regulated Target G1/S-specific cyclin-D1 (CCND1) View Details
Crosstalk Relationship m6A  →  m7G Enhancement
Crosstalk Mechanism m6A modification indirectly impacts RNA modification through downstream signaling pathways
Crosstalk Summary METTL3 interacts with hsa-miR-193b, increasing its m6A level and promoting its physical interaction with G1/S-specific cyclin-D1 (CCND1), which was regulated by METTL1-mediated m7G modification.
In-vitro Model
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
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 [4]
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
 Compound Name Briciclib Phase 1 [5]
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
 Compound Name 7-hydroxycoumarin Investigative [6]
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
 Compound Name 3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione Investigative [7]
Synonyms
CHEMBL380598; SCHEMBL3148490; HVQJGNALTWNDMX-UHFFFAOYSA-N; BDBM50375058; 2-(1H-Indole-3-yl)-3-phenylmaleimide
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MOA Inhibitor
External Link
 Compound Name 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Investigative [7]
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
 Compound Name 3,4-diphenyl-1H-pyrrole-2,5-dione Investigative [7]
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
 Compound Name 3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione Investigative [7]
Synonyms
CHEMBL372076; SCHEMBL3822337
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MOA Inhibitor
External Link
 Compound Name 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Investigative [8]
MOA Inhibitor
External Link
References
Ref 1 Overexpressed methyltransferase-like 1 (METTL1) increased chemosensitivity of colon cancer cells to cisplatin by regulating miR-149-3p/S100A4/p53 axis. Aging (Albany NY). 2019 Dec 20;11(24):12328-12344. doi: 10.18632/aging.102575. Epub 2019 Dec 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 Methylation-associated silencing of miR-193b improves the radiotherapy sensitivity of esophageal cancer cells by targeting cyclin D1 in areas with zinc deficiency. Radiother Oncol. 2020 Sep;150:104-113. doi: 10.1016/j.radonc.2020.06.022. Epub 2020 Jun 21.
Ref 4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 5 Clinical pipeline report, company report or official report of Onconova.
Ref 6 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 7 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 8 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.