M6A-modified circArhgap26 attenuates cardiac ischemia‒reperfusion injury by suppressing plakophilin-1 palmitoylation - PubMed

4 hours ago

Cardiac ischemia-reperfusion (I/R) injury is a major cause of disability and mortality worldwide.
CircArhgap26, a circular RNA regulated by m6A modification, was found to be significantly decreased in I/R myocardium.
Overexpression of circArhgap26 improved cardiac function, reduced infarct area, and decreased cardiomyocyte apoptosis in I/R model mice.
Mechanistically, circArhgap26 binds to PKP1, inhibiting its interaction with palmitoyltransferase ZDHHC1, leading to reduced PKP1 palmitoylation and stability.
This reduction in PKP1 stability decreases APAF1 protein synthesis and inhibits the Caspase-9/Caspase-3 signaling pathway, mitigating apoptosis.
CircArhgap26 levels were also decreased in the plasma of patients undergoing percutaneous coronary intervention (PCI).
The study highlights circArhgap26's dual regulatory mechanisms via m6A modification and palmitoylation, offering potential as a prognostic biomarker and therapeutic target.

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