Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, China.
Eur Rev Med Pharmacol Sci. 2020 Apr;24(7):3882-3891. doi: 10.26355/eurrev_202004_20854.
The aim of this study was to screen differentially expressed micro ribonucleic acids (miRNAs) in the plasma of patients with cerebral infarction (CI). In addition, the role of miR-150-5p in the incidence of CI is mainly explored via animal models and molecular biology experiments.
Blood samples were collected from hospitalized patients diagnosed with CI, including 15 CI patients and 15 non-CI patients as negative controls. Differentially expressed miRNAs in the plasma of these subjects were screened by microarray analysis. TargetScan was applied to predict the target genes of miR-150-5p, which were subjected to GO and pathway enrichment analyses using WebGestalt. Sprague-Dawley rats were randomly divided into Sham group (n=20), Control group (n=20), and Experimental group (n=20). CI model in rats was established in the latter two groups. Rats in Experimental group and Control group were intravenously injected with miR-150-5p mimics or miR-negative control (NC), respectively. The expressions of vital genes in the Wnt signaling pathway, including p53, Cyclin D1 (CCND1), c-Myc, β-catenin (CTNNB1) and Survivin were detected by Western blot in rats at 3 d after injection.
A total of 3,568 differentially expressed miRNAs were detected in the peripheral blood between CI patients and controls, whose 2,100 were upregulated, including miR-150-5p (p<0.05). The target genes of miR-150-5p were involved in molecular pathways, such as the Wnt signaling pathway, carcinogenesis, endocrine regulation, and infection. Compared with rats in Control group, the protein expression of p53 was downregulated (p<0.05), while CCND1, c-Myc, CTNNB1 and Survivin were upregulated (p<0.05) in Experimental group.
MiR-150-5p regulates the Wnt signaling pathway and participates in cell proliferation and apoptosis by downregulating p53, which may be a potential mechanism of CI induction.
本研究旨在筛选脑梗死（CI）患者血浆中差异表达的微小核糖核酸（miRNA）。此外，主要通过动物模型和分子生物学实验探索 miR-150-5p 在 CI 发病中的作用。
收集住院 CI 患者和 15 例非 CI 患者（阴性对照）的血样，通过微阵列分析筛选受试者血浆中差异表达的 miRNA。应用 TargetScan 预测 miR-150-5p 的靶基因，采用 WebGestalt 进行 GO 和通路富集分析。将 Sprague-Dawley 大鼠随机分为假手术组（n=20）、对照组（n=20）和实验组（n=20）。后两组建立大鼠 CI 模型。实验组和对照组大鼠分别静脉注射 miR-150-5p 模拟物或 miR-阴性对照（NC）。注射后 3d，通过 Western blot 检测大鼠 Wnt 信号通路中关键基因 p53、细胞周期蛋白 D1（CCND1）、c-Myc、β-连环蛋白（CTNNB1）和 Survivin 的表达。
CI 患者与对照组外周血中检测到 3568 个差异表达 miRNA，其中 2100 个上调，包括 miR-150-5p（p<0.05）。miR-150-5p 的靶基因参与了分子途径，如 Wnt 信号通路、致癌作用、内分泌调节和感染。与对照组大鼠相比，实验组大鼠 p53 蛋白表达下调（p<0.05），而 CCND1、c-Myc、CTNNB1 和 Survivin 蛋白表达上调（p<0.05）。
miR-150-5p 通过下调 p53 调节 Wnt 信号通路，参与细胞增殖和凋亡，可能是 CI 发病的潜在机制。
