Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02227
[1], [2]
DNA methylation DNMT3A METTL14 Direct Inhibition m6A modification hsa-miR-146a-5p hsa-miR-146a-5p METTL14 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
m6A Target hsa-miR-146a-5p
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator Cysteine methyltransferase DNMT3A (DNMT3A) WRITER View Details
Regulated Target Methyltransferase-like protein 14 (METTL14) View Details
Crosstalk Relationship DNA methylation  →  m6A Inhibition
Crosstalk Mechanism DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary lncRNA UCA1 recruited DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. In breast cancer, hsa-miR-146a-5p modulated by METTL14 promoted cell migration and invasion.
Responsed Disease Breast cancer ICD-11: 2C60
Cell Process Cell migration and invasion
Epithelial-mesenchymal transition
In-vitro Model
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Cysteine methyltransferase DNMT3A (DNMT3A) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PMID27376512-Compound-Figure3CN Patented [3]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
 Compound Name PMID27376512-Compound-Figure3CG Patented [3]
MOA Inhibitor
Activity EC50 = 2400 nM
External Link
 Compound Name PMID27376512-Compound-Figure3CM Patented [3]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
 Compound Name PMID27376512-Compound-Figure2aExample1 Patented [3]
MOA Inhibitor
Activity IC50 = 3000 nM
External Link
 Compound Name PMID27376512-Compound-MTC-424 Patented [3]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
 Compound Name PMID27376512-Compound-MTC-427 Patented [3]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
 Compound Name PMID27376512-Compound-MTC-422 Patented [3]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
 Compound Name PMID27376512-Compound-MTC-423 Patented [3]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
2C60: Breast cancer 2 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Entrectinib Approved [4]
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 [5]
External Link
References
Ref 1 LncRNA UCA1 promotes SOX12 expression in breast cancer by regulating m(6)A modification of miR-375 by METTL14 through DNA methylation. Cancer Gene Ther. 2022 Jul;29(7):1043-1055. doi: 10.1038/s41417-021-00390-w. Epub 2022 Jan 13.
Ref 2 METTL14 promotes the migration and invasion of breast cancer cells by modulating N6?methyladenosine and hsa?miR?146a?5p expression. Oncol Rep. 2020 May;43(5):1375-1386. doi: 10.3892/or.2020.7515. Epub 2020 Feb 24.
Ref 3 DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. doi: 10.1080/13543776.2016.1209488. Epub 2016 Jul 18.
Ref 4 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 5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015