Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05218
[1]
Non-coding RNA miR-532-5p METTL3  lncRNA       miRNA   circRNA Direct Inhibition m6A modification ARHGAP5 ARHGAP5 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target Rho GTPase activating protein 5 (ARHGAP5)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator hsa-miR-532-5p microRNA View Details
Regulated Target Methyltransferase-like protein 3 (METTL3) View Details
Crosstalk Relationship ncRNA  →  m6A Inhibition
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary ADAR1 edits METTL3 mRNA and changes its binding site to hsa-miR-532-5p, leading to increased METTL3 protein, which further targets Rho GTPase activating protein 5 (ARHGAP5), recognized by YTHDF1.
Responsed Disease Breast cancer ICD-11: 2C60
Cell Process Proliferation
migration
invasion
In-vitro Model
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
In-vivo Model Roughly 1 × 107 of MCF-7 or MDA-MB-231 cells stably transfected with ADAR1 sgRNA or Ctrl sgRNA (as described above) were injected subcutaneously into the thighs of the female athymic nude mice (5 weeks old, 17-18 g, three mice per group).
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
    Click to Show/Hide
External Link
 Compound Name Everolimus Approved [3]
External Link
References
Ref 1 RNA Editing Enzyme ADAR1 Regulates METTL3 in an Editing Dependent Manner to Promote Breast Cancer Progression via METTL3/ARHGAP5/YTHDF1 Axis. Int J Mol Sci. 2022 Aug 25;23(17):9656. doi: 10.3390/ijms23179656.
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