m6A-centered Crosstalk Information
Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
| Crosstalk ID |
M6ACROT03104
|
[1] | |||
Histone modification
PLK3
SETDB1
Downstream Gene
Indirect
Enhancement
m6A modification
LINC00115
LINC00115
ALKBH5
Demethylation
 : m6A sites
|
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| m6A Modification: | |||||
|---|---|---|---|---|---|
| m6A Regulator | RNA demethylase ALKBH5 (ALKBH5) | ERASER | |||
| m6A Target | long intergenic non-protein coding RNA 115 (LINC00115) | ||||
| Epigenetic Regulation that have Cross-talk with This m6A Modification: | |||||
| Epigenetic Regulation Type | Histone modification (HistMod) | ||||
| Epigenetic Regulator | Histone-lysine N-methyltransferase SETDB1 (SETDB1) | WRITER | View Details | ||
| Regulated Target | Polo like kinase 3 (PLK3) | View Details | |||
| Crosstalk Relationship | Histone modification → m6A | Enhancement | |||
| Crosstalk Mechanism | histone modification indirectly regulates m6A modification through downstream signaling pathways | ||||
| Crosstalk Summary | Polo like kinase 3 (PLK3) methylation decreases PLK3 phosphorylation of HIF1alpha and thereby increases HIF1alpha stability. HIF1alpha, in turn, upregulates ALKBH5 to reduce m6A modification of Long intergenic non-protein coding RNA 115 (LINC00115), resulting in attenuated degradation of YTHDF2-dependent m6A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1alpha are prognostic for clinical triple-negative breast cancers. | ||||
| Responsed Disease | Triple-negative breast cancer | ICD-11: 2C6Z | |||
| Responsed Drug | Acetaminophen | ||||