Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, No 6, Shuangyong Road, Nanning, Guangxi, China.
J Mol Neurosci. 2014 Jan;52(1):148-55. doi: 10.1007/s12031-013-0155-9. Epub 2013 Oct 30.
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.
微小 RNA 是一种调节基因表达的小非编码 RNA 分子，miR-124 是大脑中最丰富的 miRNA。研究表明，中风后缺血性大脑中 miR-124 明显减少；然而，miR-124 中风后的作用研究较少。我们使用 TargetScan、MicroCosm Targets version 5 和 microRNA.org 数据库，将 miR-124 鉴定为 DNA 修复蛋白 Ku70 的潜在调节因子。我们通过荧光素酶报告活性测定验证了 Ku70 是 miR-124 的靶标。此外，局灶性脑缺血的成年大鼠表现出 miR-124 表达的大量减少，而 Ku70 表达则呈负相关上调。体内用 miR-124 拮抗剂治疗可有效增强缺血区 Ku70 mRNA 和蛋白水平。此外，脑内 miR-124 的敲低可减少细胞死亡和梗死面积，改善神经功能结局。我们的数据表明，miR-124 是 Ku70 的内源性调节剂，可改善缺血/再灌注（I/R）引起的脑损伤和功能障碍。
