Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05565
[1]
m6A modification KRT7-AS KRT7-AS METTL3 Methylation : m6A sites Direct Enhancement Non-coding RNA KRT7-AS KRT7  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target KRT7-AS
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator KRT7-AS LncRNA View Details
Regulated Target Keratin, type II cytoskeletal 7 (KRT7) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary Specifically, increased METTL3 methylated Keratin, type II cytoskeletal 7 (KRT7)-AS at A877 to increase the stability of a KRT7-AS/KRT7 mRNA duplex via IGF2BP1/HuR complexes. m6A promotes breast cancer lung metastasis by increasing the stability of a KRT7-AS/KRT7 mRNA duplex and translation of KRT7.
Responsed Disease Breast cancer ICD-11: 2C60
In-vitro Model
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
In-vivo Model First, subcutaneous transplanted model was used to evaluate the growth of BT-549LMF3 and BT-549 cells. Cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Second, subcutaneous transplanted model was used to evaluate the metastasis potential of BT-549LMF3 and BT-549 cells. Cells (5 × 106 per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Third, the in vivo lung metastasis model was established by injecting with BT-549, BT-549LMF3, FTO stable BT-549LMF3, sh-METTL3 BT-549LMF3, and sh-KRT7 BT-549LMF3 stable cells (1 × 106 per mouse, n = 5 for each 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 N(6) -Methyladenosine Regulates mRNA Stability and Translation Efficiency of KRT7 to Promote Breast Cancer Lung Metastasis. Cancer Res. 2021 Jun 1;81(11):2847-2860. doi: 10.1158/0008-5472.CAN-20-3779. Epub 2021 Apr 1.
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