Abstract:

Objective To investigate the level and clinical value of serum miRNA-148a in patients with acute ischemic stroke (AIS). Methods The serum samples of peripheral blood from 42 AIS patients and 42 healthy control participants were collected, and the miRNA-148a levels of all subjects were measured by a realtime fluorogenic quantitative PCR. The receiver operating characteristic (ROC) curve of miRNA- 148a for the diagnosis of AIS was plotted, and the correlation between miRNA-148a expressioin level and clinical data were analyzed. The GSE55937 dataset were downloaded from Gene Expression Omnibus to measure the miRNA-148a expression level in AIS patients, and the target genes and biological functions of miRNA-148a were predicted using bioinformatics analysis. Results The miRNA-148a expression level in AIS patients within 12 h after onset was significantly lower than that in healthy control group (0.76±0.23 vs 1.02±0.21, P <0.001).The area under the ROC curve of miRNA-148a for the diagnosis of AIS was 0.79 (95%CI 0.70-0.89, P <0.001). Spearman correlation test showed that the miRNA-148a expression level in AIS patients were negatively associated with infarction size (r =-0.34, P =0.03) and high sensitivity C-reactive protein (hs-CRP) (r =-0.43, P =0.005). In GSE55937 dataset, the level of miRNA-148a was also remarkably lower in AIS than that in control group (1.93±0.46 vs 2.52±1.00, P =0.011), and the area under the ROC curve of miRNA-148a for the diagnosis of AIS was 0.69 (95%CI 0.54-0.84, P =0.022). A total of 58 target genes were predicted by bioinformatics methods, such as WNT10B and DNMT1. The molecular mechanism of the target genes mainly involve the regulation of cell apoptosis, FoxO signaling pathway and PI3K-Akt pathway and etc. Conclusions The serum miRNA-148a level is significantly decreased in the early phase of AIS patients, and the mechanism of miRNA-148a in stroke may involve cell apoptosis, FoxO signal pathway and PI3K-Akt signal pathway. miRNA-148a may have certain value in the diagnosis and assessment of AIS.

Key words: Ischemic stroke; miRNA-148a; Biomarker; Bioinformatics

摘要：

目的 探讨急性缺血性卒中（acute i schemi c stroke，AI S）患者血清mi RNA-148a的表达水平及其临床 价值。 方法 收集42例AIS患者和42例健康者的外周血血清样本，采用实时定量聚合酶链反应技术测定 miRNA-148a的表达水平。绘制miRNA-148a对AIS诊断的受试者工作特征（receiver operating characteristic， ROC）曲线，并分析mi RNA-148a与临床资料的相关性。从基因表达综合数据库下载GSE55937数据集对 AIS患者的miRNA-148a水平进行进一步验证，并采用生物信息学方法预测其靶基因及生物功能。 结果 AIS患者发病12 h内的miRNA-148a相对表达量低于健康对照组（0.76±0.23 vs 1.02±0.21， P <0.001）。mi RNA-148a诊断AI S的ROC曲线下面积为0.79（95%CI 0.70～0.89，P <0.001）。Spearman相 关性检验表明，mi RNA-148a水平与AIS患者的脑梗死面积（r =-0.34，P =0.03）和hs-CRP水平（r =- 0.43，P =0.005）负相关。在GSE55937数据集中，mi RNA-148a相对表达量在AIS组也明显低于对照组 （1.93±0.46 vs 2.52±1.00，P =0.011），其对AIS诊断的ROC曲线下面积为0.69（95%CI 0.54～0.84， P =0.022)。生物信息学方法共预测到58个miRNA-148a的靶基因，包括WNT10B、DNMT1等。这些靶基因 主要涉及的分子机制包括调控细胞凋亡、FoxO信号通路、PI3K-Akt通路等。 结论 AIS患者发病早期的血清miRNA-148a水平降低，可能涉及细胞凋亡和FoxO、PI3K-Akt等信号通 路，提示mi RNA-148a可能在AIS的诊断及病情评估方面具有一定参考价值。

关键词: 缺血性卒中; mi RNA-148a; 标志物; 生物信息学