m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05957
 [1]
Histone modification ALKBH7 PRMT5 Downstream Gene Indirect Enhancement m6A modification BRCA1 BRCA1 ALKBH5 Demethylation : m6A sites
m6A Modification:
m6A Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
m6A Target Breast cancer type 1 susceptibility protein (BRCA1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Protein arginine N-methyltransferase 5 (PRMT5) WRITER View Details
Regulated Target Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial (ALKBH7) View Details
Crosstalk Relationship Histone modification  →  m6A Enhancement
Crosstalk Mechanism Histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary PRMT5 inhibited doxorubicin-induced RNA m6A methylation by enhancing the nuclear translocation of ALKBH5 with the partner Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial (ALKBH7). ALKBH5 removed m6A methylation from Breast cancer type 1 susceptibility protein (BRCA1) mRNA, maintained BRCA1 stability and function, and thereby reduced cell sensitivity to doxorubicin. The approved drug tadalafil as a novel PRMT5 inhibitor that could decrease RNA m6A methylation and increase doxorubicin sensitivity in breast cancer.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Tadalafil
 Drug Info 
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Cell proliferation
DNA repair
In-vitro Model
 MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2C60: Breast cancer 2 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Entrectinib Approved [2]
Synonyms
1108743-60-7; RXDX-101; UNII-L5ORF0AN1I; Entrectinib (RXDX-101); L5ORF0AN1I; Benzamide, N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methyl-1-piperazinyl)-2-[(tetrahydro-2H-pyran-4-yl)amino]-; Benzamide, N-(5-((3,5-difluorophenyl)methyl)-1H-indazol-3-yl)-4-(4-methyl-1-piperazinyl)-2-((tetrahydro-2H-pyran-4-yl)amino)-; Entrectinib [USAN:INN]; YMX; Kinome_2659; Entrectinib(rxdx-101); Entrectinib (USAN/INN); SCHEMBL3512601; GTPL8290; CHEMBL1983268; KS-00000TSK
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External Link
CID: 25141092
TTD: D0O0LS
DrugBank: DB11986
 Compound Name Everolimus Approved [3]
External Link
CID: 6442177
TTD: D09ZSC
DrugBank: DB01590
References
Ref 1 PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer. Mol Ther. 2022 Jul 6;30(7):2603-2617. doi: 10.1016/j.ymthe.2022.03.003. Epub 2022 Mar 10.
Ref 2 Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372... Cancer Discov. 2017 Apr;7(4):400-409.
Ref 3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015