MicroRNA-128-3p Protects Mouse Against Cerebral Ischemia Through Reducing p38α 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 down-regulation 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.