m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT03119
|
[1] | |||
Histone modification
H3K4me3
WDR5
ALKBH5
Direct
Enhancement
m6A modification
PAK5
PAK5
ALKBH5
Demethylation
 : m6A sites
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| m6A Modification: | |||||
|---|---|---|---|---|---|
| m6A Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | |||
| m6A Target | Serine/threonine-protein kinase PAK 6 (PAK5) | ||||
| 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 | Enhancement | |||
| Crosstalk Mechanism | histone modification directly impacts m6A modification through modulating the level of m6A regulator | ||||
| Crosstalk Summary | E7 increased ALKBH5 expression through E2F1-mediated activation of the Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of Serine/threonine-protein kinase PAK 6 (PAK5). The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Our data provide evidence that E2F1 promotes ALKBH5 transcription by the p300-mediated H3K27ac and WDR5-mediated H3K4me3 mechanisms. | ||||
| Responsed Disease | Cervical cancer | ICD-11: 2C77 | |||
In-vitro Model |
C-33 A | Cervical squamous cell carcinoma | Homo sapiens | CVCL_1094 | |
| HeLa | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | ||
| SiHa | Cervical squamous cell carcinoma | Homo sapiens | CVCL_0032 | ||
| Ca Ski | Cervical squamous cell carcinoma | Homo sapiens | CVCL_1100 | ||
| In-vivo Model | Tumor xenograft models were established, with each group consisting of 5 mice (n = 5 per group), including ALKBH5, ALKBH5/shPAK5, NC, shCon, shPAK5, shALKBH5, and shALKBH5. Subcutaneous injections of stably transfected HeLa cells (2.0 × 106 cells) were administered into the armpit region of the nude mice. | ||||
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 | [2] | |
|---|---|---|---|---|
| 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
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| MOA | Antagonist | |||
| External Link | ||||
References