m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03404
 [1], [2]
Histone modification H3K27ac p300 ALKBH5 Direct Enhancement m6A modification SIRT3 SIRT3 ALKBH5 Demethylation : m6A sites
m6A Modification:
m6A Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
m6A Target NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3)
 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 Enhancement
Crosstalk Mechanism histone modification directly impacts m6A modification through modulating the level of m6A regulator
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.ALKBH5 demethylates and destabilizes NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) in an m6A-IGF2BP1-dependent manner, repressing CESC growth, lipid metabolism and tumorigenesis by downregulating ACC1.
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
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
Ect1/E6E7 Normal Homo sapiens CVCL_3679
In-vivo Model The animals were maintained in pathogen-free conditions at 21 ° C ± 2 ° C and 55% ± 5% humidity with free access to food and water. Mice were randomly divided into three groups (n = 8 per group) and received a subcutaneous injection of 2 × 106 stably transfected SiHa cells containing the indicated lentivirus (empty, Lv-ALKBH5, Lv-ALKBH5 + Lv-ACC1) diluted in PBS in the left flank. The mice were sacrificed when tumours were apparent on day 30. Tumour volume was recorded 7, 14, 21 and 28 days after injection with a Vernier calliper. After euthanasia, xenografts were excised from mice and weighed.
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 ALKBH5 inhibits the SIRT3/ACC1 axis to regulate fatty acid metabolism via an m6A-IGF2BP1-dependent manner in cervical squamous cell carcinoma. Clin Exp Pharmacol Physiol. 2023 May;50(5):380-392. doi: 10.1111/1440-1681.13754. Epub 2023 Feb 18.
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.