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MiR-641 Exacerbates the Progression of Ischemic Stroke Through the MCL-1/Wnt/β-Catenin Pathway by Qi Pan, Kaixuan Li, Linxia Xue, Xiaoyi Cheng, Qi Zhou

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 cerebrovascular 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 development. 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 oxygen-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 analysis 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/β-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 expression were decreased, along with increased miR-641 expression, cell apoptosis, and inflammation. MiR-641 aggravated 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/β-catenin pathway.
Conclusions: MiR-641 may be a novel therapeutic agent for ischemic stroke by modulating the MCL-1/Wnt/β-catenin axis on neuronal damage in brain tissue in the ischemic region after ischemic stroke.

DOI: 10.7754/Clin.Lab.2021.210834