MicroRNA-29c Correlates with Neuroprotection Induced by FNS by Targeting Both Birc2 and Bak1 in Rat Brain after Stroke
MicroRNA-29c Correlates with Neuroprotection Induced by FNS by Targeting Both Birc2 and Bak1 in Rat Brain after Stroke
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DOI：
10.1111/cns.12383
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发表时间：
2015-06-01
影响因子：
5.5
通讯作者：
Liu, Jing-Li
中科院分区：
文献类型：
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作者：
Huang, Li-Gang;Li, Jin-Pin;Liu, Jing-Li
目的研究表明，电刺激小脑顶核可减轻脑损伤，但其神经保护机制尚不完全清楚；microRNAs是以转录后方式调节基因表达的非编码RNA分子，但其在脑缺血再灌注(IR)后的功能影响尚不清楚。目的探讨microRNA-29c在FNS诱导的大鼠IR模型中的作用。此外，在建立IR模型前1d，左脑室内注入miR-29c抗凝剂(或异丙咪胺或对照组)。RT-qPCR检测BIRC2、Bak1mRNA和miR-29c在不同组间的差异表达。用免疫印迹法检测BIRC2蛋白和Bak1蛋白在不同组间的表达差异。结果FNS后MiR-29c表达下降，MIR-29c表达下降。此外，miR-29c直接与Birc2和Bak1基因预测的3-UTR靶点结合。此外，miR-29c的过度表达可有效降低BIRC2和Bak1的mRNA和蛋白水平，增加梗塞体积和细胞凋亡率，恶化神经预后，而下调表达则起到神经保护作用。结论miR-29c通过负调控BIRC2和Bak1参与FNS诱导的神经保护作用。
AimsStudies showed fastigial nucleus stimulation (FNS) reduced brain damage, but the mechanisms of neuroprotection induced by FNS were not entirely understood; MicroRNAs are noncoding RNA molecules that regulate gene expression in a posttranscriptional manner, but their functional consequence in response to ischemia-reperfusion (IR) remains unknown. We investigated the role of microRNA-29c in the neuroprotection induced by FNS in rat.MethodsThe IR rat models were conducted 1day after FNS. Besides, miR-29c antagomir (or agomir or control) was infused to the left intracerebroventricular 1day before IR models were conducted. We detected differential expression of Birc2 mRNA (also Bak1mRNA and miR-29c) level among different groups by RT-qPCR. The differential expression of Birc2 protein (also Bak1 protein) level among different groups was surveyed via Western blot. The neuroprotective effects were assessed by infarct volume, neurological deficit, and apoptosis.ResultsMiR-29c was decreased after FNS. Moreover, miR-29c directly bound to the predicted 3-UTR target sites of Birc2and Bak1 genes. Furthermore, over-expression of miR-29c effectively reduced Birc2 (also Bak1) mRNA and protein levels, increased infarct volume and apoptosis, and deteriorated neurological outcomes, whereas down-regulation played a neuroprotective role.ConclusionsMiR-29c correlates with the neuroprotection induced by FNS by negatively regulating Birc2 and Bak1.