The Long Non-coding RNA SNHG12 Functions as a Competing Endogenous RNA to Modulate the Progression of Cerebral Ischemia/Reperfusion Injury.

Increasing research has proved that long non-coding RNAs (lncRNAs) play a critical role in a variety of biological processes. However, their functions in cerebral ischemia are still unclear. We found that the small nucleolar RNA host gene 12 (SNHG12) is a new type of lncRNA induced by ischemia/reperfusion. Here, we show that the expression of SNHG12 was upregulated in the brain tissue of mice exposed to middle cerebral artery occlusion/reperfusion (MCAO/R) and primary mouse cerebral cortex neurons treated with oxygen-glucose deprivation/reoxygenation (OGD/R). Mechanistically, SNHG12 knockdown resulted in larger infarct sizes and worse neurological scores in MCAO/R mice. Consistent with the in vivo results, SNHG12 upregulation significantly increased the viability and prevented apoptosis of neurons cultured under OGD/R conditions. In addition, we found that SNHG12 acts as a competing endogenous RNA (ceRNA) with microRNA (miR)-136-5p, thereby regulating the inhibition of its endogenous target Bcl-2. Moreover, SNHG12 was proven to target miR-136-5p, increasing Bcl-2 expression, which finally led to the activation of PI3K/AKT signaling. In conclusion, we demonstrated that SNHG12 acts as a ceRNA of miR-136-5p, thereby targets and regulates the expression of Bcl-2, which attenuates cerebral ischemia/reperfusion injury via activation of the PI3K/AKT pathway. This knowledge helps to better understand the pathophysiology of cerebral ischemic stroke and may provide new treatment options for this disease.