LncRNA SNHG12 as a potent autophagy inducer exerts neuroprotective effects against cerebral ischemia/reperfusion injury.

Long-non-coding RNA small nucleolar RNA host gene 12(SNHG12) was reported to be highly up-regulated in brain microvascular endothelium after cerebral ischemia. Autophagy has been shown to have protective effects against cerebral ischemic insults. However, molecular mechanisms of SNHG12 in regulating autophagy during cerebral ischemia/reperfusion (I/R) injury remain unclear. Here, we established middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice and adopted oxygen-glucose deprivation and reperfusion (OGD/R) SH-SY5Y cell model to mimic cerebral I/R injury in vitro. Triphenyltetrazolium chloride (TTC) staining was used to measure infarct size. Bederson and Longa score systems were used to evaluate neurological behavioral and defects, respectively. CCK-8, EdU staining, flow cytometry and Hoechst 33258 staining were performed to determine the biological function of SNHG12 on SH-SY5Y cell under OGD/R condition. The autophagy levels were determined by Western blotting and LC3B immunofluorescence. We found the expression of SNHG12 was up-regulated by cerebral I/R in mice andSH-SY5Y cell model after OGD/R. Up-regulated SNHG12 alleviated OGD/R-induced SH-SY5Y cell injury and induced autophagy activation, as indicated by an increased ratio of LC3 II/I and Beclin-1, decreased p62. On the contrary, down-regulation of SNHG12 exacerbated SH-SY5Y cell injury after OGD/R and inhibited autophagy. Furthermore, autophagy activator rapamycin or inhibitor 3-MA partially reversed the down-regulation or up-regulation of SNHG12 effect in OGD/R-inducedSH-SY5Y cell injury, respectively. Taken together, these findings suggest that SNHG12 as an autophagy inducer alleviates cerebral I/R injury, which might be a new therapeutic target of ischemic stroke.