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双相障碍患者外周长链非编码 RNA 的表达。

Peripheral expression of long non-coding RNAs in bipolar patients.

机构信息

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Affect Disord. 2019 Apr 15;249:169-174. doi: 10.1016/j.jad.2019.02.034. Epub 2019 Feb 11.

Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) have established roles in the pathogenesis of diverse human disorders including neuropsychiatric disorders.

METHODS

In the current study, we evaluated expression levels of six apoptosis-related lncRNAs (CCAT2, TUG1, PANDA, NEAT1, FAS-AS1 and OIP5-AS1) in the peripheral blood of bipolar disorder (BD) patients and healthy subjects to assess their contribution in the pathogenesis of BD.

RESULTS

CCAT2, TUG1 and PANDA were up-regulated in total BD patients compared with total healthy subjects (P values = 0.006, <0.001 and 0.004 respectively) while OIP5-AS1 was down-regulated (P = 0.001). When expression levels of these genes were compared between patients and sex-matched healthy subjects, CCAT2 and TUG1 expression levels were only different in male subgroups; while PANDA expression was different in both male and female subgroups compared with the corresponding control subgroups. Transcript levels of lncRNAs were not correlated with any of demographic or clinical parameters of BD patients or controls after adjustment for gender. Pairwise correlations between expression levels of lncRNAs followed a disease-dependent manner. Based on receiver operating characteristic curves, among the assessed lncRNAs TUG1 had the highest diagnostic power in BD. Combination of transcript levels of CCAT2, TUG1, PANDA and OIP5-AS1 improved both sensitivity and specificity resulting in diagnostic power of 0.96.

CONCLUSION

Our data demonstrated a possible role of certain lncRNAs in the pathogenesis of BD and potentiated them as diagnostic markers in this disorder.

摘要

背景

长链非编码 RNA(lncRNA)在包括神经精神疾病在内的多种人类疾病的发病机制中发挥着重要作用。

方法

在本研究中,我们评估了六种与细胞凋亡相关的 lncRNA(CCAT2、TUG1、PANDA、NEAT1、FAS-AS1 和 OIP5-AS1)在双相情感障碍(BD)患者和健康受试者外周血中的表达水平,以评估它们在 BD 发病机制中的作用。

结果

与健康受试者相比,总 BD 患者中 CCAT2、TUG1 和 PANDA 的表达上调(P 值分别为 0.006、<0.001 和 0.004),而 OIP5-AS1 的表达下调(P=0.001)。当比较这些基因在患者和性别匹配的健康受试者之间的表达水平时,仅在男性亚组中 CCAT2 和 TUG1 的表达水平不同;而在男性和女性亚组中,PANDA 的表达水平与相应的对照组亚组不同。lncRNA 的转录水平与 BD 患者或对照者的任何人口统计学或临床参数均无相关性,且经性别调整后亦然。lncRNA 表达水平之间的两两相关性呈现疾病依赖性。基于接受者操作特征曲线,在评估的 lncRNA 中,TUG1 在 BD 中具有最高的诊断效能。CCAT2、TUG1、PANDA 和 OIP5-AS1 的转录水平组合可提高诊断的敏感性和特异性,使诊断效能达到 0.96。

结论

我们的数据表明,某些 lncRNA 可能在 BD 的发病机制中发挥作用,并增强了它们作为该疾病的诊断标志物的作用。

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