m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03408
 [1], [2]
Histone modification H3K4me3 WDR5 ALKBH5 Indirect Inhibition m6A modification GAS5 GAS5 YTHDF2 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
m6A Target Growth arrest specific 5 (GAS5)
 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 ALKBH5 View Details
Crosstalk Relationship Histone modification  →  m6A Inhibition
Crosstalk Mechanism histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary E7 increased ALKBH5 expression through WDR5-mediated activation of the Histone H3 lysine 27 acetylation (H3K27ac) histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner.The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway.
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
Cell Process Cell proliferation and metastasis
In-vitro Model
 Ca Ski Cervical squamous cell carcinoma Homo sapiens CVCL_1100
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
C-33 A Cervical squamous cell carcinoma Homo sapiens CVCL_1094
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
In-vivo Model 200 uL PBS containing 1× 107 cells of stable cells were subcutaneously injected into male BALB/c athymic nude mice (6-week old, 18-20 g).
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
WD repeat-containing protein 5 (WDR5) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name OICR-9429 Investigative [3]
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
    Click to Show/Hide
MOA Antagonist
External Link
CID: 91623360
TTD: D0XI3W
References
Ref 1 HPV E7-drived ALKBH5 promotes cervical cancer progression by modulating m6A modification of PAK5. Pharmacol Res. 2023 Sep;195:106863. doi: 10.1016/j.phrs.2023.106863. Epub 2023 Jul 20.
Ref 2 Long noncoding RNA GAS5-AS1 suppresses growth and metastasis of cervical cancer by increasing GAS5 stability. Am J Transl Res. 2019 Aug 15;11(8):4909-4921. eCollection 2019.
Ref 3 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).