m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT00065
 [1]
RNA modification METTL3 METTL3 ADAR1 Methylation : modification sites Direct Enhancement m6A modification ARHGAP5 ARHGAP5 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Rho GTPase activating protein 5 (ARHGAP5)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type RNA modification (RNAMod)  >> Adenosine-to-Inosine editing (A-to-I)
Epigenetic Regulator Interferon-inducible protein 4 (ADAR1) WRITER View Details
Regulated Target Methyltransferase-like protein 3 (METTL3) View Details
Crosstalk Relationship A-to-I  →  m6A Enhancement
Crosstalk Mechanism RNA modification directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary overexpression and knockdown of ADAR1 respectively increased and decreased the expression levels of METTL3 and Rho GTPase activating protein 5 (ARHGAP5) protein in breast cancer. Study demonstrate that ADAR1 promotes the proliferation, migration and invasion of breast cancer cells through the METTL3/ARHGAP5/YTHDF1 axis and establish that METTL3 is one of the main targets of ADAR1 controlling biological functions.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Cell Process Cell proliferation
Cell migration
Cell 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). Tumor growth was measured by measuring the width (W) and length (L) with calipers, and the volume (V) of the tumor was figured using the criterion V = (W2 × L)/2. At 42 days after injection, the mice were euthanized and tumors were removed and weighed. The tumor samples were further analyzed with IHC and Western blot assay. The animal studies were performed according to the institutional ethics guidelines for animal experiments and approved by the Chongqing Medical University Animal Care and Use Committee.
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
CID: 25141092
TTD: D0O0LS
DrugBank: DB11986
 Compound Name Everolimus Approved [3]
External Link
CID: 6442177
TTD: D09ZSC
DrugBank: DB01590
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