title: MicroRNA-124 (miR-124) regulates Ku70 expression and is correlated with neuronal death induced by ischemia/reperfusion.
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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, No 6, Shuangyong Road, Nanning, Guangxi, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhu
authors.forename: Jing-Li
authors.initials: JL
authors.lastname: Liu
authors.forename: Jing-Pin
authors.initials: JP
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009841:Oligonucleotides / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C548144:MIRN124 microRNA, rat; D035683:MicroRNAs; D009841:Oligonucleotides; D012333:RNA, Messenger; C000606509:Xrcc6 protein, human; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen