Clinical Significance and Mechanistic Role of circLPAR3/miR-634 in Ischemic Stroke

Individuals with hypertension carry a high risk of stroke, which endangers human health. The study systematically elucidated the dynamic expression, functional effects, and molecular mechanisms of the circular RNA LPAR3 in ischemic stroke (IS). 300 essential-hypertension (EH) patients were enrolled, comprising 165 cases diagnosed with IS. mRNA abundance was quantified via RT-qPCR. C57BL/6 mice treated with MACO and Neuro-2a cells receiving oxygen-glucose deprivation/reoxygenation (OGD/R) were applied for functional experiments. Neurological deficits and infarct volume of mice were evaluated. Besides, key cellular behaviors encompassing proliferative capacity, apoptotic rate, and inflammatory response were monitored. The putative binding event was interrogated through luciferase reporter and RIP coupled to qPCR assays. A diminished level of circLPAR3 was evidenced in the plasma of IS patients, which can distinguish IS cases from EH and remains an independent predictor of patients' poor prognosis. In vivo, overexpression of circLPAR3 alleviated MACO-mediated neurological deficit and cerebral infarction. In vitro, OGD/R triggered the surge in cell apoptosis and pro-inflammatory cytokine release, but it was attenuated by circLPAR3 upregulation. Mechanistically, the neuro-rescue driven by circLPAR3 was offset by miR-634, whose plasma expression was negatively correlated with circLPAR3. KLB expression was significantly downregulated in cellular models and co-regulated by circLPAR3 and miR-634. circLPAR3/miR-634 modulates the pathological progression of IS by directly regulating neuronal apoptosis and orchestrating inflammatory responses, and KLB may serve as a key downstream target mediating the biological functions.