m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03405
 [1], [2]
Histone modification H3K27ac p300 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 Histone acetyltransferase p300 (P300) WRITER View Details
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac) 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 p300-mediated activation of the Histone H3 lysine 4 trimethylation (H3K4me3), 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
Histone acetyltransferase p300 (P300) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CCS1477 Phase 1/2 [3]
Synonyms
CCS-1477; CBP-IN-1; 2222941-37-7; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-((1r,4S)-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one; SCHEMBL20094038; SCHEMBL21515367; SCHEMBL22134021; EX-A3687; NSC818619; NSC-818619; HY-111784; CS-0091862; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-(trans-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 134457551
TTD: DIY4C2
 Compound Name FT-7051 Phase 1 [4]
MOA Inhibitor
External Link
TTD: DT8IL6
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 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov. 2021 May;11(5):1118-1137. doi: 10.1158/2159-8290.CD-20-0751. Epub 2021 Jan 11.
Ref 4 Clinical pipeline report, company report or official report of FORMA Therapeutics.