m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02041
 [1]
m6A modification IGFBP7-OT IGFBP7-OT METTL3 Methylation : m6A sites Direct Inhibition DNA methylation DNMT3a IGFBP7
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Insulin-like Growth Factor Binding Protein 7 Overlapping Transcript
 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 Insulin-like growth factor-binding protein 7 (IGFBP7) View Details
Crosstalk Relationship m6A  →  DNA methylation Inhibition
Crosstalk Mechanism m6A modification directly impacts DNA methylation through modulating the expression level of DNA methyltransferases or demethylases.
Crosstalk Summary Insulin-like Growth Factor Binding Protein 7 Overlapping Transcript suppresses the occupancy of DNMT1 and DNMT3A on the Insulin-like growth factor-binding protein 7 (IGFBP7) promoter, thereby inhibiting methylation of the IGFBP7 promoter. The upregulation of IGFBP7-OT in OA is partially controlled by METTL3-mediated N-methyladenosine (mA) modification. Collectively, our findings reveal that mA modification of IGFBP7-OT promotes OA progression by regulating the DNMT1/DNMT3A-IGFBP7 axis and provide a potential therapeutical target for OA treatment.
Responsed Disease Oosteoarthritis ICD-11: FA0Z
 Disease Info 
Pathway Response Apoptosis hsa04210
Cell Process Cell apoptosis
In-vivo Model 8-week-old male C57BL/6 mice were randomly divided into four groups: Ctrl+AAV-NC group (n = 6), Ctrl+AAV-OT group (n = 6), MIA+AAV-NC group (n = 8), and MIA+ AAV-OT group (n = 8). For the induction of OA, mice were given an intra-articular injection of MIA (Sigma-Aldrich) in the knee. Control mice were given normal saline in the same volume.
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 [2]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117968550
TTD: D02VTV
 Compound Name PMID27376512-Compound-Figure3CG Patented [2]
MOA Inhibitor
Activity EC50 = 2400 nM
External Link
CID: 117967861
TTD: D03LZO
 Compound Name PMID27376512-Compound-Figure3CM Patented [2]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117976053
TTD: D0F8AB
 Compound Name PMID27376512-Compound-Figure2aExample1 Patented [2]
MOA Inhibitor
Activity IC50 = 3000 nM
External Link
CID: 71521835
TTD: D01LUJ
 Compound Name PMID27376512-Compound-MTC-424 Patented [2]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [2]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [2]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [2]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
References
Ref 1 METTL3-mediated m(6)A modification of IGFBP7-OT promotes osteoarthritis progression by regulating the DNMT1/DNMT3a-IGFBP7 axis. Cell Rep. 2023 Jun 27;42(6):112589. doi: 10.1016/j.celrep.2023.112589. Epub 2023 Jun 2.
Ref 2 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.