Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02028
[1]
m6A modification Circ_YTHDC2 Circ_YTHDC2 YTHDC2 : m6A sites Indirect Inhibition DNA methylation TET2 SRF
m6A Modification:
m6A Regulator YTH domain-containing protein 2 (YTHDC2) READER
m6A Target Circ_YTHDC2
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator Methylcytosine dioxygenase TET2 (TET2) ERASER View Details
Regulated Target Serum response factor (SRF) View Details
Crosstalk Relationship m6A  →  DNA methylation Inhibition
Crosstalk Mechanism m6A modification indirectly regulates DNA methylation through downstream signaling pathways
Crosstalk Summary The mechanism analysis revealed that YTHDC2-mediated m6A modification stabilized Circ_YTHDC2. In addition, circYTHDC2 negatively regulated the expression of Ten-Eleven Translocation 2 (TET2) by targeting the unstable motif of TET2 3'UTR, thereby promoting the proliferation and migration of VSMCs, and TET2 functions as an upstream regulator of MYOCD, Serum response factor (SRF) and KLF4, which are key drivers of phenotypic plasticity of VSMC. These findings suggest that the YTHDC2/circYTHDC2/TET2 pathway is an important target of metformin in preventing the progression of VSMCs dysfunction.
Responsed Disease Hematological disorders ICD-11: 3C0Z
Responsed Drug Metformin
Cell Process Cell proliferation
Cell migration
In-vitro Model
A7r5 Normal Rattus norvegicus CVCL_0137
In-vivo Model Sprague Dawley rats were anesthetized by intraperitoneal injection of 1.5% pentobarbital sodium at 0.2 mL/100 g. The thoracic aorta was separated under aseptic conditions, and was placed in pre-cooled DMEM medium, and the tunica media was separated under a microscope. The tunica media were cut into small pieces of 0.5-1 mm2, and digested with type II collagenase (2 mg/mL) in a 37 ° C water bath. The cells were collected by centrifugation, and resuspended in DMEM medium containing 20% FBS.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
3C0Z: Hematological disorders 5 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Lmw heparin Approved [2]
Synonyms
Fragmin; Heparinin; MolPort-042-652-620; Logiparin (TN); Sandoparin (TN)
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 Compound Name CK0801 Phase 1 [3]
External Link
 Compound Name HemoTech Investigative [4]
Synonyms
Blood substitute (hematological disease), HemoBiotech; Bovine hemoglobin + adenosine 5'-triphosphate + o-adenosine + reduced glutathione (hemotological disease), HemoBiotech
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 Compound Name PN-951 Investigative [4]
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 Compound Name Hematological disease agents Investigative [4]
Synonyms
Hematological disease agents, Tartis; SM-27
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References
Ref 1 YTHDC2-Mediated circYTHDC2 N6-Methyladenosine Modification Promotes Vascular Smooth Muscle Cells Dysfunction Through Inhibiting Ten-Eleven Translocation 2. Front Cardiovasc Med. 2021 Oct 1;8:686293. doi: 10.3389/fcvm.2021.686293. eCollection 2021.
Ref 2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 3 ClinicalTrials.gov (NCT03773393) A Clinical Trial of CK0801 (a New Drug) in Patients With Bone Marrow Failure Syndrome (BMF). U.S. National Institutes of Health.
Ref 4 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.