Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05593
[1]
m6A modification hsa-miR-193b hsa-miR-193b METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA miR-193b CCND1  lncRNA       miRNA   circRNA
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 Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-193b microRNA View Details
Regulated Target G1/S-specific cyclin-D1 (CCND1) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of hsa-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
Cell Process Cell proliferation
Arrest Cell cycle
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 [2]
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 [3]
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 [4]
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 [5]
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 [5]
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 [5]
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 [5]
Synonyms
CHEMBL372076; SCHEMBL3822337
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MOA Inhibitor
External Link
 Compound Name 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Investigative [6]
MOA Inhibitor
External Link
References
Ref 1 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 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 3 Clinical pipeline report, company report or official report of Onconova.
Ref 4 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 5 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 6 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.