m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05510
 [1]
m6A modification MALAT1 MALAT1 METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA MALAT1 miR-26b  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) LncRNA View Details
Regulated Target hsa-miR-26b View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary Silencing METTL3 down-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and HMGA2 by sponging hsa-miR-26b, and finally inhibit EMT, migration and invasion in breast cancer, providing a theoretical basis for clinical treatment of breast cancer.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Cell Process Cell invasion
Cell migration
Epithelial-mesenchymal transition
In-vitro Model
 MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MCF-10A Normal Homo sapiens CVCL_0598
In-vivo Model Eighteen BALB/C female nude mice (SLAC Laboratory Animal Co., Ltd., Shanghai, China) aged 4-5 weeks and weighing 15-18 g were randomly assigned into three groups of six mice. The MCF-7 cell lines stably transfected with sh-NC + oe-NC, sh-METTL3 + oe-NC and sh-METTL3 + oe-HMGA2 were selected for subcutaneous establishment of the BC cell line MCF-7 as xenografts in the nude mice. For this purpose, MCF-7 cell lines in the logarithmic growth stage were prepared into a suspension with a concentration of about 1 × 107 cells/ml.For construction of the model of lung metastasis of BC, 3 × 106 MCF-7 cells infected with sh-NC + oe-NC, sh-METTL3 + oe-NC or sh-METTL3 + oe-HMGA2 were injected into nude mice via a tail vein. After 5 weeks, the pathological changes of lung tissue were observed by hematoxylin and eosin staining (HE staining) and the metastasis of tumor nodules were observed.
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 The m6A methyltransferase METTL3 controls epithelial-mesenchymal transition, migration and invasion of breast cancer through the MALAT1/miR-26b/HMGA2 axis. Cancer Cell Int. 2021 Aug 21;21(1):441. doi: 10.1186/s12935-021-02113-5.
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