MiR-641 Exacerbates the Progression of Ischemic Stroke Through the MCL-1/Wnt/?-Catenin Pathway

Background: Ischemic stroke refers to ischemic necrosis or softening of limited brain tissue caused by ischemia and hypoxia due to impaired blood circulation in the brain. Ischemic stroke is a major classification of cerebro-vascular disease, accounting for about 80% of patients with cerebrovascular disease in China, with a high rate of disability and death. Recently, miRNAs were reported to participate in ischemic stroke pathogenesis and develop-ment. In the study, we aimed to study the role and underlying mechanism of miR-641 in ischemic stroke. Methods: Serum samples were extracted from acute ischemic stroke (AIS) patients and healthy controls. The oxy-gen-glucose deprivation/reoxygenation (OGD/R) method was used to treat SH-SY5Y cells to construct an ischemic stroke in vitro model. Real-time quantitative polymerase chain reaction (qRT-PCR) assay and western blot analy-sis were conducted to detect miR-641 and MCL-1 expressions. The targeted relationship between miR-641 and MCL-1 was confirmed by dual-luciferase reporter, RNA pull-down, and rescue assays. CCK-8, flow cytometry, and ELISA assays were performed to measure cell viability, apoptosis, and inflammation. The activation of the Wnt/beta-catenin pathway was verified by western blot assay. Results: MiR-641 was increased while MCL-1 was decreased in serum samples from AIS patients, serving as highly-sensitive biomarkers in AIS diagnosis. After OGD/R treatment, SH-SY5Y cell viability, and MCL-1 ex-pression were decreased, along with increased miR-641 expression, cell apoptosis, and inflammation. MiR-641 ag-gravated while MCL-1 mitigated OGD/R-triggered injury and inflammation in SH-SY5Y cells. MCL-1 was a downstream target of miR-641, which could be negatively regulated by miR-641. Finally, miR-641 exacerbated the progression of OGD/R-triggered SH-SY5Y cell injury via the MCL-1/Wnt/beta-catenin pathway. Conclusions: MiR-641 may be a novel therapeutic agent for ischemic stroke by modulating the MCL-1/Wnt/beta-ca-tenin axis on neuronal damage in brain tissue in the ischemic region after ischemic stroke.