MicroRNA-124 (miR-124) Regulates Ku70 Expression and is Correlated with Neuronal Death Induced by Ischemia/Reperfusion

作者:Zhu, Fei; Liu, Jing-Li*; Li, Jing-Pin; Xiao, Fang; Zhang, Zhao-Xia; Zhang, Lei
来源:Journal of Molecular Neuroscience, 2014, 52(1): 148-155.
DOI:10.1007/s12031-013-0155-9

摘要

MicroRNAs are small, non-coding RNA molecules that regulate gene expression, and miR-124 is the most abundant miRNA in the brain. Studies have shown that miR-124 is clearly reduced in the ischemic brain after stroke; however, the role of miR-124 after stroke is less well studied. Using TargetScan, MicroCosm Targets version 5, and microRNA.org databases, we identified miR-124 as a possible regulator of the DNA repair protein Ku70. We validated that Ku70 is a target for miR-124 with a luciferase reporter activity assay. Moreover, adult rats subjected to focal cerebral ischemia exhibited a substantial reduction of miR-124 expression, which was inversely upregulated by Ku70 expression. In vivo treatment with miR-124 antagomir effectively enhanced Ku70 mRNA and protein levels in the ischemic region. Furthermore, knockdown of cerebral miR-124 reduced cell death and infarct size and improved neurological outcomes. Our data demonstrate that miR-124 is an endogenous regulator of Ku70 that improves ischemia/reperfusion (I/R)-induced brain injury and dysfunction.