南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (07): 922-929.doi: 10.12122/j.issn.1673-4254.2020.07.02

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卒中后抑郁患者血浆中miR-30a-5p的差异性表达及其作用机制的生物信息学预测

胡 佳，周志明，杨 倩，杨 科   

  • 出版日期:2020-07-20 发布日期:2020-07-20
  • 基金资助:

Differential expression of miR-30a-5p in post stroke depression and bioinformatics analysis of the possible mechanism

  

  • Online:2020-07-20 Published:2020-07-20

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摘要： 目的 探讨卒中后抑郁（PSD）患者miR-30a-5p的表达差异性及其在PSD中的诊断价值，基于生物信息学方法，分析其可能作用机制。方法 检索PubMed数据库，利用VENNY2.1在线软件获取到目标microRNA。贯续性纳入2018年10月~2019年3月就诊于皖南医学院弋矶山医院神经内科卒中病房并首次诊断为急性脑梗死的患者，收集患者入院时人口统计学资料、卒中危险因素、既往卒中病史、美国国立卫生研究院脑卒中量表（NHISS）评分等临床基线资料及影像学资料，并与入院当天留取研究对象外周静脉血5 mL。随访3个月根据Hamilton 抑郁量表（HAMD-17）行抑郁程度的评价，对于评分值≥7 者按照《美国精神病学会叶精神疾病诊断与统计手册》第4 版（DSM-IV）诊断标准诊断抑郁，分为PSD组（n=11）和non-PSD组（n=25）。使用qRT-PCR法检测卒中后抑郁患者（PSD）和非卒中后抑郁患者（NPSD）外周血miR-30a-5p表达水平，利用ENCORI数据库和CTD（Comparative Toxicogenomics Database）数据库共同预测和筛选miR-30a-5p调控的抑郁相关可能作用的靶基因，通过生物信息学方法对靶基因的可能作用机制进行进一步分析。结果 通过交叉筛选得到同时与卒中和抑郁相关的 miR-30a-5p，临床样本 qRT-PCR 验证 miR-30a-5p 在 PSD 和 non-PSD 组有差异性表达（2.462±0.326 vs 1±0.126，P<0.0001）。ROC曲线分析提示miR-30a-5p预测PSD的AUC=0.869（95%CI，0.745-0.993，P=0.0005），cut-off值为1.597，对应的敏感性和特异性分别为0.727、0.840。靶蛋白主要作用的生物学过程包括信号转导、细胞间通讯、核酸碱基、核苷、核苷酸和核酸代谢的调节；KEGG通路富集分析发现，靶蛋白主要作用于神经营养素信号通路、轴突导向信号通路、胰岛素信号传导系统；经过CytoHUBBA分析得出可能与卒中后抑郁相关的前20种HUB基因。结论 外周血miR-30a-5p在卒中后抑郁患者和非卒中后抑郁患者中存在差异性表达，可以作为诊断PSD的临床标志物，其可能是通过神经营养素信号通路、轴突导向信号通路、胰岛素信号传导系统来影响PSD的发生。

关键词: 卒中后抑郁, miR-30a-5p, 生物信息学

Abstract: Objective To investigate the differential expression of miR-30a-5p in patients with poststroke depression and explore the possible mechanism. Methods We obtained the target microRNAs through searching PubMed using the online software VENNY2.1. We collected the baseline demographic, clinical and radiographic data from consecutive patients with first-ever acute ischemic stroke on admission in our department from October, 2018 to March, 2019. From each patient, 5 mL peripheral venous blood was collected upon admission. Hamilton Depression Scale (HAMD-17) was used to evaluate the degree of depression at the end of the 3-month follow-up. The patients with a HAMD-17 score≥7 were diagnosed to have depression according to the diagnostic criteria of the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-IV). The patients were divided into post-stroke depression group (PSD group, n=11) and non-post-stroke depression group (non-PSD group, n=25), and their plasma levels of miR-30a-5p were detected using qPCR. The STARBASE Database ENCORI miRNA-mRNA module and Comparative Toxicogenomics Database were used to predict and screen the possible target genes related to miR-30a-5p, and the possible mechanism of the target genes was further analyzed through bioinformatics. Results miR-30a-5p was identified by cross-screening as the target miRNA associated with stroke and depression and showed obvious differential expression between PSD and non-PSD patients (2.462±0.326 vs 1±0.126, P<0.0001). ROC curve analysis showed that the AUC of miR-30a-5p for predicting PSD was 0.869 (95%CI: 0.745-0.993, P=0.0005) at the cutoff value of 1.597, with a sensitivity and specificity of 0.727 and 0.840, respectively. The target proteins of miR-30a-5p involved a wide range of biological processes, including signal transduction, intercellular communication, regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism. KEGG pathway enrichment analysis showed that the target proteins affected mainly the neural nutrient signaling pathway, axon guidance signaling pathway and insulin signaling system. We also identified the top 20 HUB genes that might be associated with post-stroke depression. Conclusion Plasma miR-30a-5p is differentially expressed in PSD and can serve as a new blood marker for diagnosis and also a therapeutic target of PSD.

Key words: post stroke depression, miR-30a-5p; bioinformatics