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颅内动脉瘤中长链非编码RNA相关竞争性内源性RNA网络的鉴定

Identification of a Long Noncoding RNA-Associated Competing Endogenous RNA Network in Intracranial Aneurysm.

作者信息

Li Hao, Wang Wen, Zhang Lu, Lan Qing, Wang Jiangfei, Cao Yong, Zhao Jizong

机构信息

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China.

出版信息

World Neurosurg. 2017 Jan;97:684-692.e4. doi: 10.1016/j.wneu.2016.10.016. Epub 2016 Oct 15.

Abstract

BACKGROUND

Intracranial aneurysm (IA) is a cerebrovascular disorder characterized by an abnormally bulged artery in the brain and subarachnoid hemorrhage caused by IA rupture with a high ratio of fatality and morbidity. However, the genetic cause of IA remains largely unknown.

METHODS

A dysregulated long noncoding RNA (lncRNA) -associated competing endogenous RNA (ceRNA) network was constructed by using sample-matched microRNA (miRNA), lncRNA, and messenger (mRNA) expression profiles in 12 saccular IA samples and paired control arteries.

RESULTS

In this study, 1150 lncRNAs, 2545 mRNAs, and 286 miRNAs were differentially expressed in IAs compared with control arteries. Using miRanda, a ceRNA score was assigned, and gene expression methods were used to construct a ceRNA network. The network consists of 8401 miRNA-lncRNA-mRNA interactions (199 miRNAs, 445 lncRNAs, 1116 mRNAs; P < 0.05). Further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the mRNAs involved in the ceRNA network were involved in the regulation of muscle contraction and vascular smooth muscle contraction.

CONCLUSIONS

By comparing IAs and their control arteries, we identified differentially expressed lncRNAs, miRNAs, and mRNAs and suggested ceRNA roles in the pathogenesis of IA. These findings may help to characterize the pathogenesis of IA and provide novel therapeutic targets in the future for patients with IA.

摘要

背景

颅内动脉瘤(IA)是一种脑血管疾病,其特征是脑动脉异常膨出,IA破裂导致蛛网膜下腔出血,致死率和致残率很高。然而,IA的遗传病因在很大程度上仍不清楚。

方法

利用12个囊状IA样本及其配对对照动脉的样本匹配微小RNA(miRNA)、长链非编码RNA(lncRNA)和信使RNA(mRNA)表达谱构建失调的lncRNA相关竞争性内源性RNA(ceRNA)网络。

结果

在本研究中,与对照动脉相比,IA中有1150个lncRNA、2545个mRNA和286个miRNA差异表达。使用miRanda分配ceRNA评分,并使用基因表达方法构建ceRNA网络。该网络由8401个miRNA-lncRNA-mRNA相互作用组成(199个miRNA、445个lncRNA、1116个mRNA;P<0.05)。进一步的基因本体论和京都基因与基因组百科全书通路分析表明,ceRNA网络中涉及的mRNA参与肌肉收缩和血管平滑肌收缩的调节。

结论

通过比较IA及其对照动脉,我们鉴定了差异表达的lncRNA、miRNA和mRNA,并提示ceRNA在IA发病机制中的作用。这些发现可能有助于阐明IA的发病机制,并为未来IA患者提供新的治疗靶点。

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