MicroRNA-128-3p Protects Mouse Against Cerebral Ischemia Through Reducing p38[alpha] Mitogen-Activated Protein Kinase Activity

The p38[alpha], also named Mapk14, is a pro-apoptotic protein, which is reported to be downregulated 2 h after cerebral ischemia. However, little is known what causes the downregulation of p38[alpha] protein level. Here, we studied the effect of cerebral ischemia on p38[alpha] mRNA expression and p38[alpha] protein level in brain of mice. We found that p38[alpha] protein level is reduced after middle cerebral artery occlusion. However, at the meantime, p38[alpha] mRNA expression has no detectable changes, suggesting that the possible posttranscription is regulated by ischemia. To reveal the mechanism for posttranscription of p38[alpha] protein, we tested the effect of miR-128-3p. Using luciferase reporter assay, we found that miR-128-3p could directly target p38[alpha] 3'UTR. We further tested the effect of miR-128-3p on the p38[alpha] protein level. We found that miR-128-3p strongly decreased the p38[alpha] protein level in SH-SY5Y cells after the cells were transfected with miR-128-3p using lentivirus vector containing precursor its RNA sequences. We further found that inhibition of miR-128-3p enhanced the infarct volume of brain in mice. Our study thus confirms that miR-128-3p can downregulate p38[alpha] protein level through posttranscription and increase of miR-128-3p level may contribute to neuronal survival in ischemia-induced brain injury.