m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02029
 [1]
m6A modification Circ_YTHDC2 Circ_YTHDC2 YTHDC2 : m6A sites Indirect Inhibition DNA methylation TET2 KLF4
m6A Modification:
m6A Regulator YTH domain-containing protein 2 (YTHDC2) READER
 Regulator Info 
m6A Target Circ_YTHDC2
 Targert Gene 
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 Krueppel-like factor 4 (KLF4) 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, SRF and Krueppel-like factor 4 (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
 Disease Info 
Responsed Drug Metformin
 Drug Info 
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
Krueppel-like factor 4 (KLF4) 1 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name APTO-253 Phase 1 [2]
MOA Inhibitor
External Link
CID: 11960271
TTD: D07TRP
3C0Z: Hematological disorders 5 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Lmw heparin Approved [3]
Synonyms
Fragmin; Heparinin; MolPort-042-652-620; Logiparin (TN); Sandoparin (TN)
    Click to Show/Hide
External Link
CID: 25244225
TTD: D08PSU
 Compound Name CK0801 Phase 1 [4]
External Link
TTD: DX8QZ3
 Compound Name HemoTech Investigative [5]
Synonyms
Blood substitute (hematological disease), HemoBiotech; Bovine hemoglobin + adenosine 5'-triphosphate + o-adenosine + reduced glutathione (hemotological disease), HemoBiotech
    Click to Show/Hide
External Link
TTD: D0BA8H
 Compound Name PN-951 Investigative [5]
External Link
TTD: D06WLY
 Compound Name Hematological disease agents Investigative [5]
Synonyms
Hematological disease agents, Tartis; SM-27
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External Link
CID: 486047
TTD: D03BPU
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 Phase 1 study of APTO-253 HCl, an inducer of KLF4, in patients with advanced or metastatic solid tumors. Invest New Drugs. 2015 Oct;33(5):1086-92. doi: 10.1007/s10637-015-0273-z. Epub 2015 Aug 14.
Ref 3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 4 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 5 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.