Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00612
[1], [2], [3], [4]
m6A modification hsa-miR-34a hsa-miR-34a METTL14 Methylation : m6A sites Indirect Enhancement RNA modification CCNE1 CCNE1 YBX1 : modification sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
m6A Target hsa-miR-34a
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> 5-methylcytidine (m5C)
Epigenetic Regulator Y-box-binding protein 1 (YBX1) READER View Details
Regulated Target G1/S-specific cyclin-E1 (CCNE1) View Details
Crosstalk Relationship m6A  →  m5C Enhancement
Crosstalk Mechanism m6A modification indirectly impacts RNA modification through downstream signaling pathways
Crosstalk Summary METTL14 interacts with hsa-miR-34a, reading its m6A level and promoting its physical interaction with G1/S-specific cyclin-E1 (CCNE1), which was regulated by YBX1-mediated m5C modification.
In-vitro Model
U-CH1 Sacral chordoma Homo sapiens CVCL_4988
MUG-Chor1 Sacral chordoma Homo sapiens CVCL_9277
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
BxPC-3 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0186
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
G1/S-specific cyclin-E1 (CCNE1) 25 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PD-0183812 Terminated [5]
Synonyms
PETCVZZPKYJZAU-UHFFFAOYSA-N; PD183812; AC1NS8PJ; CHEMBL139653; SCHEMBL5268115; BDBM6280; PD 0183812; N8 Pyrido[2,3-d]pyrimidin-7-one deriv 72; 8-{bicyclo[221]heptan-2-yl}-2-({4-[4-(3-hydroxypropyl)piperidin-1-yl]phenyl}amino)-7H,8H-pyrido[2,3-d]pyrimidin-7-one; 8-(3-bicyclo[221]heptanyl)-2-[4-[4-(3-hydroxypropyl)piperidin-1-yl]anilino]pyrido[2,3-d]pyrimidin-7-one; PD0183813
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MOA Inhibitor
External Link
 Compound Name (2'Z,3'E)-5-Chloro-5'-chloro-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
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 Compound Name (2'Z,3'E)-5-Chloro-5'-methyl-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
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 Compound Name (2'Z,3'E)-5-Fluoro-5'-methoxy-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
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 Compound Name (2'Z,3'E)-5-Fluoro-5'-fluoro-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
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 Compound Name (2'Z,3'E)-5-Fluoro-5'-chloro-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
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 Compound Name (2'Z,3'E)-5-Chloro-5'-fluoro-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
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 Compound Name 2-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol Investigative [7]
MOA Inhibitor
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 Compound Name 5-nitroindirubin-3'-oxime Investigative [6]
MOA Inhibitor
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 Compound Name (2'Z,3'E)-5-Nitro-5'-methyl-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
External Link
 Compound Name (2'Z,3'E)-5-Nitro-5'-chloro-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
External Link
 Compound Name (2'Z,3'E)-5-Fluoro-5'-hydroxy-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
External Link
 Compound Name (2'Z,3'E)-5-Chloro-5'-hydroxy-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
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 Compound Name (2'Z,3'E)-5-Nitro-5'-fluoro-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
External Link
 Compound Name (2'Z,3'E)-5-Nitro-5'-methoxy-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
External Link
 Compound Name (2'Z,3'E)-5-Fluoro-5'-methyl-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
External Link
 Compound Name (2'Z,3'E)-5-Nitro-5'-hydroxy-indirubin-3'-oxime Investigative [6]
MOA Inhibitor
External Link
 Compound Name 3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol Investigative [7]
MOA Inhibitor
External Link
 Compound Name aloisine A Investigative [8]
Synonyms
4-(7-butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)phenol; 496864-16-5; RP107; 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE; CHEMBL75680; 7-n-Butyl-6-(4-hydroxyphenyl)[5H]pyrrolo[2,3-b]pyrazine; RP-107; ALH; 4-{7-butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl}phenol; 1ung; SCHEMBL80147; BDBM7377; GTPL5924; AC1NS169; 4-(7-Butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenol; CHEBI:93641; CTK8D4068; DTXSID30416115; HMS3229A14; RM-39; BCP26893; ZINC2540737; ACT06534; IN1539; HSCI1_000219; MFCD04973541; AKOS005145972; CCG-206814; DB07364; RTC-063070; AJ-39131
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MOA Inhibitor
External Link
 Compound Name 3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione Investigative [9]
Synonyms
CHEMBL380598; SCHEMBL3148490; HVQJGNALTWNDMX-UHFFFAOYSA-N; BDBM50375058; 2-(1H-Indole-3-yl)-3-phenylmaleimide
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MOA Inhibitor
External Link
 Compound Name BMS-536924 Investigative [10]
MOA Inhibitor
External Link
 Compound Name 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Investigative [9]
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 [9]
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 [9]
Synonyms
CHEMBL372076; SCHEMBL3822337
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MOA Inhibitor
External Link
 Compound Name 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Investigative [7]
MOA Inhibitor
External Link
References
Ref 1 Y-box binding protein-1 promotes tumorigenesis and progression via the epidermal growth factor receptor/AKT pathway in spinal chordoma. Cancer Sci. 2019 Jan;110(1):166-179. doi: 10.1111/cas.13875. Epub 2018 Dec 19.
Ref 2 Overexpression of YBX1 Promotes Pancreatic Ductal Adenocarcinoma Growth via the GSK3B/Cyclin D1/Cyclin E1 Pathway. Mol Ther Oncolytics. 2020 Mar 29;17:21-30. doi: 10.1016/j.omto.2020.03.006. eCollection 2020 Jun 26.
Ref 3 N6-Methyladenosine Induced miR-34a-5p Promotes TNF-alpha-Induced Nucleus Pulposus Cell Senescence by Targeting SIRT1. Front Cell Dev Biol. 2021 Mar 5;9:642437. doi: 10.3389/fcell.2021.642437. eCollection 2021.
Ref 4 CircDENND2A Promotes Non-small Cell Lung Cancer Progression via Regulating MiR-34a/CCNE1 Signaling. Front Genet. 2020 Sep 1;11:987. doi: 10.3389/fgene.2020.00987. eCollection 2020.
Ref 5 Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16. doi: 10.1021/jm000271k.
Ref 6 5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity. J Med Chem. 2010 May 13;53(9):3696-706. doi: 10.1021/jm100080z.
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 Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003 Jan 16;46(2):222-36. doi: 10.1021/jm020319p.
Ref 9 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 10 Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. J Med Chem. 2005 Sep 8;48(18):5639-43. doi: 10.1021/jm050392q.