MicroRNA-3571 attenuates ferroptosis-induced damage by modulating ALOX15 expression in PC12 cells and rat models of acute ischemic stroke.

Acute ischemic stroke (AIS) is a severe neurological condition with high disability and mortality rates. Ferroptosis, an iron-dependent form of regulated cell death, plays a key role in ischemic brain injury, but its exact regulatory mechanisms in AIS are still unclear. Using a rat middle cerebral artery occlusion/reperfusion (MCAO/R) model and PC12 cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, we found that ALOX15 is upregulated and miR-3571 is downregulated in AIS, correlating with increased ferroptosis and neuronal injury. We confirmed that miR-3571 directly targets the 3'-UTR of ALOX15 mRNA, thereby suppressing its expression. In vivo, miR-3571 overexpression reduced infarct volume, improved neurological function, and inhibited ferroptosis; in vitro, miR-3571 mimics enhanced viability and suppressed ferroptosis. ALOX15 silencing replicated these protective effects, and combining miR-3571 overexpression with ALOX15 knockdown conferred no added benefit, indicating that miR-3571 acts primarily through ALOX15 inhibition. Thus, the miR-3571/ALOX15 axis is a novel ferroptosis-regulating pathway in AIS, positioning miR-3571 as a promising therapeutic target.