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

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Abstract

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.

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, No 6, Shuangyong Road, Nanning, Guangxi, China

    Fei Zhu, Jing-Li Liu, Jing-Pin Li, Fang Xiao, Zhao-Xia Zhang & Lei Zhang

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  1. Fei Zhu
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  2. Jing-Li Liu
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  3. Jing-Pin Li
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  4. Fang Xiao
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  5. Zhao-Xia Zhang
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  6. Lei Zhang
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Correspondence to Jing-Li Liu.

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Zhu, F., Liu, JL., Li, JP. et al. MicroRNA-124 (miR-124) Regulates Ku70 Expression and is Correlated with Neuronal Death Induced by Ischemia/Reperfusion. J Mol Neurosci 52, 148–155 (2014). https://doi.org/10.1007/s12031-013-0155-9

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  • DOI: https://doi.org/10.1007/s12031-013-0155-9

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