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双相情感障碍中DISC2长链非编码RNA表达显著增加作为一种潜在生物标志物

Significant increasing of DISC2 long non-coding RNA expression as a potential biomarker in bipolar disorder.

作者信息

Naghavi-Gargari Bahar, Zahirodin Alireza, Ghaderian Sayyed Mohammad Hossein, Shirvani-Farsani Zeinab

机构信息

Department of Basic Science, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran.

Behavioral Science Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran.

出版信息

Neurosci Lett. 2019 Mar 23;696:206-211. doi: 10.1016/j.neulet.2018.12.044. Epub 2018 Dec 29.

DOI:10.1016/j.neulet.2018.12.044
PMID:30599263
Abstract

Bipolar disorder (BD) is a mental disorder that is often misdiagnosed with ineffective treatment. It has strong genetic component but unknown pathophysiology. Long non-coding RNAs (lncRNAs) have been recently recognized as one of the important genetic factors and are considered as one of the regulatory mechanisms of nervous system. Given that lncRNAs may be diagnostic biomarkers for BD, we aimed to quantify the levels of DISC1 and DISC2 lncRNA transcripts. The levels of DISC1 and DISC2 lncRNA were tested in peripheral blood mononuclear cells (PBMCs) of 50 BD and 50 controls by real-time PCR. In addition, we performed ROC curve analysis as well as correlation analysis between the gene expression and some clinical features of BD cases. Computational analysis of miRNAs binding sites and CpG Islands on DISC1 and DISC2 lncRNA was performed as well. Significant down-regulation of DISC1 and up-regulation of DISC2 were observed in BD cases compared with controls. The areas under the ROC curve (AUC) for DISC1 and DISC2 lncRNA were 0.76 and 0.68 respectively. There was no significant correlation between the levels of mRNA expression in PBMCs of BD patients and clinical features. These data demonstrated that DISC1 and DISC2 lncRNA expression was potentially associated with an increased risk of bipolar disorder and might involve several molecular mechanisms. Our results revealed that the transcript levels of DISC1 and DISC2 lncRNA could be considered as a good putative biomarker for individuals with bipolar disorder.

摘要

双相情感障碍(BD)是一种常被误诊且治疗效果不佳的精神障碍。它具有很强的遗传成分,但病理生理学尚不清楚。长链非编码RNA(lncRNAs)最近被认为是重要的遗传因素之一,并被视为神经系统的调节机制之一。鉴于lncRNAs可能是双相情感障碍的诊断生物标志物,我们旨在量化DISC1和DISC2 lncRNA转录本的水平。通过实时PCR检测了50例双相情感障碍患者和50例对照者外周血单个核细胞(PBMCs)中DISC1和DISC2 lncRNA的水平。此外,我们进行了ROC曲线分析以及双相情感障碍患者基因表达与一些临床特征之间的相关性分析。还对DISC1和DISC2 lncRNA上的miRNA结合位点和CpG岛进行了计算分析。与对照组相比,双相情感障碍患者中观察到DISC1显著下调和DISC2上调。DISC1和DISC2 lncRNA的ROC曲线下面积(AUC)分别为0.76和0.68。双相情感障碍患者PBMCs中mRNA表达水平与临床特征之间无显著相关性。这些数据表明,DISC1和DISC2 lncRNA表达可能与双相情感障碍风险增加相关,并可能涉及多种分子机制。我们的结果显示,DISC1和DISC2 lncRNA的转录水平可被视为双相情感障碍个体的良好潜在生物标志物。

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