m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02250
 [1], [2]
DNA methylation DNMT3A METTL14 Direct Inhibition m6A modification SQSTM1 SQSTM1 METTL14 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
m6A Target Sequestosome-1 (SQSTM1)
 Targert Gene 
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. METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and Sequestosome-1 (SQSTM1), thus enhancing their mRNA stability. The chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase .the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice.
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Paclitaxel
 Drug Info 
In-vitro Model
 HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model The experimental mice were housed in an SPF-grade animal laboratory at a temperature of approximately 25 ° C, a humidity range of 50%, and an average daylight duration of 12 h. BALB/C female mice at 5-6 weeks of age were taken and prepared for tumor-bearing. After the mice were sacrificed, their tissues were collected, weighed and immediately snap-frozen in liquid nitrogen.
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
CID: 117968550
TTD: D02VTV
 Compound Name PMID27376512-Compound-Figure3CG Patented [3]
MOA Inhibitor
Activity EC50 = 2400 nM
External Link
CID: 117967861
TTD: D03LZO
 Compound Name PMID27376512-Compound-Figure3CM Patented [3]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117976053
TTD: D0F8AB
 Compound Name PMID27376512-Compound-Figure2aExample1 Patented [3]
MOA Inhibitor
Activity IC50 = 3000 nM
External Link
CID: 71521835
TTD: D01LUJ
 Compound Name PMID27376512-Compound-MTC-424 Patented [3]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [3]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [3]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [3]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
Sequestosome-1 (SQSTM1) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name IMX-942 Preclinical [4]
Synonyms
IDR-1; IMX-001; IMX-502; IMX-502001; IMX-503; IMX-602; IMX-602001; IMX-606; IMX-606001; IMX-735; IMX-775; Innate immune system upregulators, Inimex; Innate defense-regulatory peptides (infection), Ininmex
    Click to Show/Hide
MOA Regulator (upregulator)
External Link
TTD: D02NEZ
2C60: Breast cancer 2 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Entrectinib Approved [5]
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 [6]
External Link
CID: 6442177
TTD: D09ZSC
DrugBank: DB01590
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 XBP1s activates METTL3/METTL14 for ER-phagy and paclitaxel sensitivity regulation in breast cancer. Cancer Lett. 2024 Aug 1;596:216846. doi: 10.1016/j.canlet.2024.216846. Epub 2024 Apr 4.
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 Clinical pipeline report, company report or official report of SARomics Biostructures.
Ref 5 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 6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015