m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02004
 [1]
DNA methylation DNMT3A SOCS3 Indirect Enhancement m6A modification COL5A2 COL5A2 YTHDF1 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
m6A Target Collagen alpha-2(V) chain (COL5A2)
 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 Suppressor of cytokine signaling 3 (SOCS3) View Details
Crosstalk Relationship DNA methylation  →  m6A Enhancement
Crosstalk Mechanism DNA methylation indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary In this study, we demonstrate that 5mC-mediated Suppressor of cytokine signaling 3 (SOCS3) suppression by DNMT3A leads to STAT3 activation. STAT3 transactivates HIF-1alpha, and HIF-1alpha subsequentially transactivates YTHDF1. YTHDF1 upregulates COL1A1, COL1A2, COL3A1, Collagen alpha-2(V) chain (COL5A2), and COL6A2, thus linking the 5mC-mediated initiation stage and the m6A-dependent perpetuation stage of the HSC activation cascade.
Responsed Disease Hepatic fibrosis/cirrhosis ICD-11: DB93
 Disease Info 
Pathway Response RNA degradation hsa03018
Cell Process mRNA stability
In-vitro Model
JS1
 N.A. Mus musculus CVCL_C7PL
In-vivo Model Following 1 week of adaptive feeding, the mice were randomly divided into CCl4 + siCON and CCl4 + siYTHDF1 groups. Both groups were injected intraperitoneally with 5 ml/kg of 10% carbon tetrachloride (CCl4) twice a week for 4 weeks, to establish liver fibrosis.
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
DB93: Hepatic fibrosis/cirrhosis 5 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name KB174 Clinical Trial [3]
External Link
TTD: DDNL40
 Compound Name Quinazoline derivative 12 Patented [4]
Synonyms
PMID26936077-Compound-23
    Click to Show/Hide
External Link
CID: 60163336
TTD: D0EC3H
 Compound Name Quinazoline derivative 10 Patented [4]
Synonyms
PMID26936077-Compound-21
    Click to Show/Hide
External Link
CID: 6737869
TTD: D0CM5P
 Compound Name Quinazoline derivative 11 Patented [4]
Synonyms
PMID26936077-Compound-22
    Click to Show/Hide
External Link
CID: 60163203
TTD: D08ZEM
 Compound Name PMID27998201-Compound-5 Patented [5]
External Link
CID: 46202117
TTD: D05OIU
References
Ref 1 DNA 5mC and RNA m(6)A modification successively facilitates the initiation and perpetuation stages of HSC activation in liver fibrosis progression. Cell Death Differ. 2023 May;30(5):1211-1220. doi: 10.1038/s41418-023-01130-3. Epub 2023 Feb 25.
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.
Ref 3 ClinicalTrials.gov (NCT03855956) Clinical Food Study to Evaluate the Effect of KB174 on the Gut Microbiome in Subjects With Well-compensated Cirrhosis. U.S. National Institutes of Health.
Ref 4 Protease activated receptor 2 (PAR2) modulators: a patent review (2010-2015).Expert Opin Ther Pat. 2016;26(4):471-83.
Ref 5 Cathepsin B and L inhibitors: a patent review (2010 - present). Expert Opin Ther Pat. 2017 Jun;27(6):643-656. doi: 10.1080/13543776.2017.1272572. Epub 2016 Dec 23.