miR-212-5p protects the brain against ischemic damage in rats and its function is regulated by the lncfos/miR-212-5p/CASP7 axis

Abstract miR-212-5p has been reported to be involved in many biological processes. However, the role of miR-212-5p in ischemic stroke remains unclear. This study aimed to explore the biological role and potential mechanism of miR-212-5p inbrain damage in rats with ischemic stroke by investigating the lncfos/miR-212-5p/CASP7 axis. Rats were subjected to middle cerebral artery occlusion (MCAO) and intracerebroventricular injection of miRNA agomir, miRNA antagomir, shRNA lentiviral vector or negative control. The neurological deficit score, infarct volume and histopathology, neuronal apoptosis, lncfos, miR-212-5p and CASP7 expression in the peri-infarct area were assessed. In this study, we found thatthe expression level of miR-212-5p was significantly downregulated in the peri-infarct area and blood in MCAO rats and in the blood of patients with ischemic stroke. The double luciferase experiment showed that CASP7 was the direct target gene of miR-212-5p and that lncfos was the direct target gene of miR-212-5p. Lateral ventricular injection of miR-212-5p agomir can effectively inhibit apoptosis induced by ischemic brain damage, reduce infarct volume, improve neurological deficit symptoms and downregulate the expression of CASP7 in the peri-infarct area in MCAO rats. Suppressing lncfos with sh-fos can upregulate the expression of miR-212-5p and plays a neuroprotective role in rat MCAO models. We conclude that miR-212-5p plays a neuroprotective role in rat MCAO models and that its function is regulated by the lncfos/miR-212-5p/CASP7 axis.