Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150001, China.
Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, 150001, China.
Int J Biol Sci. 2018 Oct 19;14(13):1791-1799. doi: 10.7150/ijbs.25352. eCollection 2018.
In recent years, accumulating evidence has revealed that microRNAs play critical roles in ischemia stroke. This study was designed to investigate the expression level and effects of microRNA (miR)-186-5p on ischemia stroke, and its underlying molecular mechanism. Firstly, we demonstrated that miR-186-5p were significantly up-regulated and induced apoptosis in oxygen and glucose deprivation/reperfusion (OGD/R) model. Moreover, we found that miR-186-5p reduced the expression of insulin-like growth factor (IGF)-1, an essential factor for the development of the nervous system. Meanwhile, miR-186-5p inhibitor enhanced cell viability and IGF-1 expression. Furthermore, IGF-1 was confirmed as a direct target gene of miR-186-5p by luciferase activity assay. In addition, miR-186-5p was upregulated in ischemia stroke patients' serum compared with healthy donors. These data demonstrated that miR-186-5p was an adverse factor by inducing neuron apoptosis and suppressing IGF-1 in ischemia stroke model, and suggested that miR-186-5p may be a diagnostic marker and potential therapeutic target for ischemia stroke patients.
近年来，越来越多的证据表明 microRNAs 在缺血性中风中发挥着关键作用。本研究旨在探讨 microRNA（miR）-186-5p 对缺血性中风的表达水平和作用及其潜在的分子机制。首先，我们证明 miR-186-5p 在氧葡萄糖剥夺/再灌注（OGD/R）模型中显著上调并诱导细胞凋亡。此外，我们发现 miR-186-5p 降低了胰岛素样生长因子（IGF）-1 的表达，IGF-1 是神经系统发育的重要因素。同时，miR-186-5p 抑制剂增强了细胞活力和 IGF-1 的表达。此外，通过荧光素酶活性测定证实 IGF-1 是 miR-186-5p 的直接靶基因。此外，与健康供体相比，缺血性中风患者血清中 miR-186-5p 水平升高。这些数据表明，miR-186-5p 通过诱导神经元凋亡和抑制 IGF-1 在缺血性中风模型中是一种不利因素，并提示 miR-186-5p 可能是缺血性中风患者的诊断标志物和潜在治疗靶点。
