• Qie Liu, Lu Zhang, and Xin Xu.
• Department of Neurology, Daqing Oilfield General Hospital, Daqing City, Heilongjiang Province, China. Electronic address: Ms.liuqieo9wu4@outlook.com.
• Clinics (Sao Paulo). 2025 Jan 29; 80: 100581100581.

ObjectiveThe authors explored differentially expressed circRNAs in Acute Ischemic Stroke (AIS) and revealed the role and potential downstream molecular mechanisms of circLOC375190.MethodscircLOC375190 expression was modulated by lentiviral injection in the brain of transient Middle Cerebral Artery Occlusion (tMCAO) mice. Neurological dysfunction was assessed, as well as infarction size, histopathological changes, and neuronal apoptosis in tMCAO mice. An in vitro Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) PC-12 cell model was established. PC-12 cells were transfected and evaluated for viability, cytotoxicity, apoptosis, and autophagy. Inflammatory factors in mouse brain tissues and PC-12 cells were examined via enzyme-linked immunosorbent assay, and related genes were measured via real-time reverse transcriptase-polymerase chain reaction and Western blot. The ring structure of circLOC375190 was assessed by actinomycin-D and RNase-R assays. circRNA targeting to downstream factors was assessed by Fluorescence in situ hybridization assay, dual luciferase reporter assay, and RNA immunoprecipitation assay.ResultscircLOC375190 level was increased in tMCAO mice. Knocking down circLOC375190 reduced infarct size, attenuated cerebral pathological injury and neuronal apoptosis, and inhibited inflammatory damage and autophagy in tMCAO mice. circLOC375190 knockdown enhanced neuronal viability and reduced cytotoxicity, apoptosis, and autophagy in OGD/R-treated PC12 cells. Mechanistically, circLOC375190 acted as a sponge for miR-93-5p to upregulate MAP kinase interacting serine/threonine kinase 2 expression and activate the mechanistic target of rapamycin complex 1/transcription factor EB pathway.ConclusioncircLOC375190 exacerbates tMCAO-mediated neurological injury by regulating neuronal autophagy.Copyright © 2025. Published by Elsevier España, S.L.U.

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