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人类颅内动脉瘤中长链非编码 RNA 的表达谱:一项微阵列分析。

Expression profile of long noncoding RNAs in human cerebral aneurysms: a microarray analysis.

机构信息

Department of Neurosurgery and.

China National Clinical Research Center for Neurological Diseases.

出版信息

J Neurosurg. 2017 Nov;127(5):1055-1062. doi: 10.3171/2016.9.JNS16839. Epub 2016 Dec 23.

Abstract

OBJECTIVE The pathogenesis of cerebral aneurysms (CAs) remains largely unknown. Long noncoding RNAs (lncRNAs) were reported recently to play crucial roles in many physiological and biological processes. Here, the authors compared the gene-expression profiles of CAs and their control arteries to investigate the potential functions of lncRNAs in the formation of CAs. METHODS A prospective case-control study was designed to identify the changes in expression of lncRNAs and mRNAs between 12 saccular CA samples (case group) and 12 paired superficial temporal artery samples (control group). Microarray analysis was performed to investigate the expression of lncRNAs and messenger RNAs (mRNAs), and reverse-transcription quantitative polymerase chain reaction was used to validate the microarray analysis findings. Then, an lncRNA target-prediction program and gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied to explore potential lncRNA functions. RESULTS A comparison between the case and control groups revealed that 1518 lncRNAs and 2545 mRNAs were expressed differentially. By using target-prediction program analysis, the authors constructed a complex network consisting of 2786 matched lncRNA-mRNA pairs, in which ine1 mRNA was potentially targeted by one to tens of lncRNAs, and vice versa. The results of further gene ontology and KEGG pathway analyses indicated that lncRNAs were involved mainly in regulating immune/inflammatory processes/pathways and vascular smooth muscle contraction, both of which are known to have crucial pathobiological relevance in terms of CA formation. CONCLUSIONS By comparing CAs with their control arteries, the authors created an expression profile of lncRNAs in CAs and propose here their possible roles in the pathogenesis of CAs. The results of this study provide novel insight into the mechanisms of CA pathogenesis and shed light on developing new therapeutic intervention for CAs in the future.

摘要

目的 脑动脉瘤(CAs)的发病机制在很大程度上尚不清楚。长链非编码 RNA(lncRNA)最近被报道在许多生理和生物学过程中发挥关键作用。在这里,作者比较了 CAs 和其对照动脉的基因表达谱,以研究 lncRNA 在 CAs 形成中的潜在功能。

方法 设计了一项前瞻性病例对照研究,以确定 12 个囊状 CA 样本(病例组)和 12 对颞浅动脉样本(对照组)之间 lncRNA 和信使 RNA(mRNA)表达的变化。进行微阵列分析以研究 lncRNA 和信使 RNA(mRNA)的表达,并使用逆转录定量聚合酶链反应验证微阵列分析结果。然后,应用 lncRNA 靶预测程序和基因本体论和京都基因与基因组百科全书(KEGG)途径分析来探讨潜在的 lncRNA 功能。

结果 病例组和对照组之间的比较显示,有 1518 个 lncRNA 和 2545 个 mRNA 表达差异。通过使用靶预测程序分析,作者构建了一个由 2786 个匹配的 lncRNA-mRNA 对组成的复杂网络,其中 ine1 mRNA 可能被一个到几十个 lncRNA 靶向,反之亦然。进一步的基因本体论和 KEGG 途径分析结果表明,lncRNA 主要参与调节免疫/炎症过程/途径和血管平滑肌收缩,这两者在 CA 形成方面具有重要的病理生物学相关性。

结论 通过比较 CAs 与其对照动脉,作者创建了 CAs 中 lncRNA 的表达谱,并提出了它们在 CAs 发病机制中的可能作用。本研究的结果为 CA 发病机制提供了新的见解,并为未来开发针对 CA 的新治疗干预措施提供了思路。

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