Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05512
[1]
m6A modification hsa-miR-143-3p hsa-miR-143-3p KIAA1429 Methylation : m6A sites Direct Inhibition Non-coding RNA Pri-miR-143-3p DDX6  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Protein virilizer homolog (VIRMA) WRITER
m6A Target hsa-miR-143-3p
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator pri-miR-143 microRNA View Details
Regulated Target DEAD-box helicase 6 (DDX6) View Details
Crosstalk Relationship m6A  →  ncRNA Inhibition
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary KIAA1429 is downregulated while ALKBH5 is upregulated in aortic tissues from aortic dissection patients. KIAA1429/ALKBH5-mediated m6A modifications can regulate the processing of hsa-miR-143-3p through interacting with the microprocessor protein DGCR8. KIAA1429 and ALKBH5 can oppositely regulate HASMC proliferation, HAEC apoptosis, and AD progression in AngII-infused mice via the miR-143-3p/DEAD-box helicase 6 (DDX6) pathway.
Responsed Disease Aortic aneurysm or dissection ICD-11: BD50
Cell Process Cell proliferation
Cell apoptosis
In-vitro Model
iHAEC Normal Homo sapiens CVCL_C0EQ
HASMCs (Human Aortic Smooth Muscle Cells)
In-vivo Model Osmotic mini-pumps containing AngII (1 ug/kg/min, Enzo Bioche) were implanted in 7-week-old male mice. To interfere with the expression of KIAA1429, ALKBH5, or DDX6 in vivo, adeno-associated virus 9 (AAV9) vectors carrying a variety of overexpression plasmids or interfering RNA were randomly injected through the tail vein to C57BL/6N mice.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
BD50: Aortic aneurysm or dissection 3 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name CRD-007 Phase 2 [2]
External Link
 Compound Name WAY-644 Investigative [3]
Synonyms
MMP-12 inhibitor (aortic abdominal aneurysm), Pfizer; MMP-12 inhibitor (aortic abdominal aneurysm), Wyeth
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External Link
 Compound Name VDA-1124 Investigative [4]
Synonyms
Granzyme B inhibitors (abdominal aortic aneurysms), viDA Therapeutics
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External Link
References
Ref 1 KIAA1429 and ALKBH5 Oppositely Influence Aortic Dissection Progression via Regulating the Maturation of Pri-miR-143-3p in an m6A-Dependent Manner. Front Cell Dev Biol. 2021 Aug 19;9:668377. doi: 10.3389/fcell.2021.668377. eCollection 2021.
Ref 2 ClinicalTrials.gov (NCT01540604) CRD007 for the Treatment of Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and Symptomatic Carriers. U.S. National Institutes of Health.
Ref 3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1636).
Ref 4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2369).