m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT03515
|
[1], [2] | |||
Histone modification
H3K27ac
P300
METTL3
Direct
Enhancement
m6A modification
LINC00426
LINC00426
METTL3
Methylation
 : m6A sites
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| m6A Modification: | |||||
|---|---|---|---|---|---|
| m6A Regulator | Methyltransferase-like 3 (METTL3) | WRITER | |||
| m6A Target | long intergenic non-protein coding RNA 426 (LINC00426) | ||||
| 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 | METTL3 | 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 | The transcription factor ETS1 recruited p300 and WDR5 which separately mediated Histone H3 lysine 27 acetylation (H3K27ac) and H3K4me3 histone modification in the promoter of METTL3 and induced METTL3 transcription activation. Furthermore, we identified TXNDC5 as a target of METTL3-mediated m6A modification through MeRIP-seq, and revealed that METTL3-mediated TXNDC5 expression relied on the m6A reader-dependent manner. METIL3 is believed to enhance the expression of Long intergenic non-protein coding RNA 426 (LINC00426) through m6A methylation modification.The LINC00426/miR-200a-3p/ZEB1 axis plays a crucial role in regulating E-cadherin, N-cadherin and vimentin during EMT in CC.Overexpression of LINC00426 in CC cells caused resistance to Cisplatin and Bleomycin, but sensitivity to imatinib. | ||||
| Responsed Disease | Cervical cancer | ICD-11: 2C77 | |||
| Responsed Drug | Imatinib | ||||
In-vitro Model |
HeLa | Endocervical adenocarcinoma | Homo sapiens | CVCL_0030 | |
| C-33 A | Cervical squamous cell carcinoma | Homo sapiens | CVCL_1094 | ||
| SiHa | Cervical squamous cell carcinoma | Homo sapiens | CVCL_0032 | ||
| In-vivo Model | HeLa cells were stably transfected with LINC00426 overexpression lentivirus. Subsequently, for subcutaneously implanted tumor model, mice were randomly divided into two groups, and cells (1 × 107/100 μ l) mixed with the same volume of matrix gel were injected subcutaneously into the right abdomen of mice. One month later the mice were executed and the tumors were stripped and weighed, measured for volume, and used for further analysis. For tumor metastasis assay, mice were randomly grouped, and 5 × 105/100 μ l HeLa cells transfected with NC and LINC00426 overexpression lentivirus were intravenously injected into the tail vein of BALB/c nude mice which were sacrificed after 1 month. | ||||
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
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| MOA | Inhibitor | |||
| External Link | ||||
| Compound Name |
FT-7051 | Phase 1 | [4] | |
| MOA | Inhibitor | |||
| External Link | ||||
References