MicroRNA-135a alleviates oxygen-glucose deprivation and reoxygenation-induced injury in neurons through regulation of GSK-3β/Nrf2 signaling

MicroRNAs (miRNAs) have been suggested as pivotal regulators in the pathological process of cerebral ischemia and reperfusion injury. In this study, we aimed to investigate the role of miR-135a in regulating neuronal survival in cerebral ischemia and reperfusion injury using an in vitro cellular model induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Our results showed that miR-135a expression was significantly decreased in neurons with OGD/R treatment. Overexpression of miR-135a significantly alleviated OGD/R-induced cell injury and oxidative stress, whereas inhibition of miR-135a showed the opposite effects. Glycogen synthase kinase-3 (GSK-3) was identified as a potential target gene of miR-135a. miR-135a was found to inhibit GSK-3 expression, but promote the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and downstream signaling. However, overexpression of GSK-3 significantly reversed miR-135a-induced neuroprotective effect. Overall, our results suggest that miR-135a protects neurons against OGD/R-induced injury through downregulation of GSK-3 and upregulation of Nrf2 signaling.