Hu Jia, Zhou Zhiming, Yang Qian, Yang Ke
Department of Neurology, Yijishan Hospital Affiliated to Wannan Medical College, Wuhu 241001, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2020 Jul 30;40(7):922-929. doi: 10.12122/j.issn.1673-4254.2020.07.02.
To investigate the differential expression of miR-30a-5p in patients with poststroke depression and explore the possible mechanism.
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, =11) and non-post-stroke depression group (non-PSD group, =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.
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 1±0.126, < 0.0001). ROC curve analysis showed that the AUC of miR-30a-5p for predicting PSD was 0.869 (95%: 0.745-0.993, =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.
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.
探讨miR-30a-5p在脑卒中后抑郁患者中的差异表达，并探索其可能的机制。
我们通过在线软件VENNY2.1在PubMed上搜索获得目标微小RNA。收集了2018年10月至2019年3月期间在我科连续入院的首次急性缺血性脑卒中患者的基线人口统计学、临床和影像学数据。每位患者入院时采集5 mL外周静脉血。采用汉密尔顿抑郁量表（HAMD-17）在3个月随访结束时评估抑郁程度。根据美国精神医学协会《精神疾病诊断与统计手册》第四版（DSM-IV）的诊断标准，HAMD-17评分≥7分的患者被诊断为患有抑郁症。将患者分为脑卒中后抑郁组（PSD组，n = 11）和非脑卒中后抑郁组（非PSD组，n = 25），采用qPCR检测他们血浆中miR-30a-5p的水平。利用STARBASE数据库的ENCORI miRNA-mRNA模块和比较毒理基因组学数据库预测和筛选与miR-30a-5p相关的可能靶基因，并通过生物信息学进一步分析靶基因的可能机制。
通过交叉筛选确定miR-30a-5p为与卒中和抑郁相关的靶微小RNA，且在PSD患者和非PSD患者之间表现出明显的差异表达（2.462±0.326 vs 1±0.126，P < 0.0001）。ROC曲线分析显示，在截断值为1.597时，miR-30a-5p预测PSD的AUC为0.869（95%CI：0.745 - 0.993，P = 0.0005），敏感性和特异性分别为0.727和0.840。miR-30a-5p的靶蛋白涉及广泛的生物学过程，包括信号转导、细胞间通讯、核碱基、核苷、核苷酸和核酸代谢调控等。KEGG通路富集分析表明靶蛋白主要影响神经营养信号通路、轴突导向信号通路和胰岛素信号系统。我们还确定了可能与脑卒中后抑郁相关的前20个HUB基因。
血浆miR-30a-5p在PSD中存在差异表达，可作为诊断的新血液标志物及PSD的治疗靶点。
