title: MicroRNA-146a down-regulation correlates with neuroprotection and targets pro-apoptotic genes in cerebral ischemic injury in vitro.
abstract: MicroRNAs (miRNAs) are short, non-coding RNAs that negatively regulate target gene expression, and play an important role in cerebral ischemic injury. MiR-146a has been reported to be highly related to cell invasion, metastasis, immunity, inflammation and apoptosis. Previous studies have indicated that miR-146a can either inhibit or promote apoptosis through different pathophysiological processes. In our previous study, miR-146a in the blood was down-regulated during acute ischemic stroke. However, the connection between miR-146a and acute cerebral ischemic injury and the mechanism underlying the connection remain unclear. Here, we aimed to investigate the role of miR-146a and its possible target genes in human SK-N-SH cells subjected to 16h of oxygen-glucose deprivation and 12h of reperfusion (OGD/R) injury. Cells were transfected with miR-146a mimic or inhibitor to alter the expression of miR-146a. MiR-146a in the SK-N-SH cells was down-regulated after OGD/R injury. Moreover, bioinformatics analysis and dual luciferase assays demonstrated that miR-146a directly recognized the 3'-UTR of the pro-apoptotic genes, Caspase7 and Bcl-2-associated transcription factor 1 (Bclaf1). Furthermore, miR-146a over-expression effectively decreased the mRNA and protein expression of Caspase7 and Bclaf1, and aggravated OGD/R-induced cell apoptosis; in contrast, miR-146a down-regulation was neuroprotective. In conclusion, our study revealed that miR-146a contributes to OGD/R injury in vitro, while negatively regulating the pro-apoptotic genes, Caspase7 and Bclaf1. This special mechanism provides new insight into miRNA regulatory networks. In addition, miR-146a may offer a potential therapeutic approach to cerebral ischemic injury.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Shengyou
authors.initials: S
authors.lastname: Su
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurology, The First People's Hospital of Nanning, Guangxi Medical University, Nanning 530021, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Chunyong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Jinpin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China. Electronic address: lilicomet@163.com.
authors.forename: Jingli
authors.initials: J
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D002545:Brain Ischemia / Q000473:pathology* / Q000628:therapy; D053179:Caspase 7 / Q000378:metabolism; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D000066829:Neuroprotection; D018696:Neuroprotective Agents; D010100:Oxygen / Q000378:metabolism; D012097:Repressor Proteins; D020521:Stroke / Q000473:pathology; D025521:Tumor Suppressor Proteins
chemical_list: D020413:3' Untranslated Regions; C119386:BCLAF1 protein, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D018696:Neuroprotective Agents; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D053179:Caspase 7; D005947:Glucose; D010100:Oxygen
keywords: Apoptosis; Cerebral ischemic injury; MicroRNA-146a; Oxygen-glucose deprivation and reperfusion