MicroRNA‐454 modulates the oxidative stress and neuronal apoptosis after cerebral ischemia/reperfusion injury via targeting NADPH oxidase 4 (NOX4)

To investigate the function of miR‐454 in ischemic stroke, this study was carried out. Cerebral ischemia/reperfusion (I/R) injury animal model and a SHSY5Y cell culture model of oxygen‐glucose deprivation/reoxygenation (OGD/R) were constructed. The effects of miR‐454 were detected by evaluating the levels of biochemical markers, gene expression, and pathophysiological markers. The results showed that NOX4 level was elevated, while miR‐454 expression was reduced in I/R brain samples and in OGD/R‐treated cells. The miR‐454 agomir declined NOX4 level and reactive oxygen species (ROS) production in rats suffering from I/R. Furthermore, microRNA‐145 (miR‐454) overexpression inhibited NOX4 level and ROS production in cells treated by OGD/R and decreased luciferase activity in cells transfected with NOX4‐wild type (WT) reporter plasmid. Meanwhile, our results proved that the protected effects of miR‐454 on SH‐SY5Y cells treated by OGD/R were reversed by pcDNA‐NOX4 transfection. MiR‐454 protected animals from brain injury induced by cerebral I/R via directly regulating its target gene NOX4, illustrating a curatively potential target for treating ischemic stroke.