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基于长链非编码RNA介导的竞争性内源RNA网络鉴定与脑小血管病相关的基因和通路

Identification of genes and pathways related with cerebral small vessel disease based on a long non-coding RNA-mediated, competitive endogenous RNA network.

作者信息

Yan Hui, Yang Xiaoli, Zhao Xueman, Wang Huankun

机构信息

Department of Neurology, The People's Hospital of Yucheng, Yucheng, Dezhou, Shandong 251200, P.R. China.

出版信息

Exp Ther Med. 2018 Jul;16(1):121-126. doi: 10.3892/etm.2018.6148. Epub 2018 May 10.

Abstract

This study aimed to investigate the cerebral small vessel disease (SVD), an intrinsic disorder of the brain's perforating arterioles, which could cause serious cognitive decreasing and trigger dementia. In this study, we present a multi-step computational approach to construct a functional SVD long non-coding RNA (lncRNA)-mediated ceRNA network (LMCN) by integrating genome-wide lncRNA and mRNA expression profiles, miRNA-target interactions, and functional analyses. We used hypergeometric test to evaluate enrichment significance of miRNAs and we obtained the LMCN, which contained 27 lncRNAs, 7,229 mRNA, and 28,871 lncRNAs-mRNA interrelationship pairs. What's more, co-expression analysis was utilized to constructe a competitive endogenous RNAs (ceRNAs) interaction network which comprised of 21 lncRNAs, 129 mRNAs and 141 interaction pairs. We determined that metastasis-associated lung adenocarcinoma transcript 1 and MIR155 host gene acted synergistically to regulate mRNAs in a network module of the competitive LMCN. Moreover, 7 genes were obtained through Gene Ontology enrichment. In addition, 29 mRNA enriched pathways significantly associated with lncRNAs was obtained via Fisher test. In conclusion, we identified 7 potential lncRNAs and 29 possible lncRNA-mediated pathways associated with SVD. Thus, ceRNAs could accelerate biomarker discovery and therapeutic development in SVD.

摘要

本研究旨在调查脑小血管疾病(SVD),这是一种脑穿通小动脉的内在疾病,可导致严重的认知能力下降并引发痴呆。在本研究中,我们提出了一种多步骤计算方法,通过整合全基因组lncRNA和mRNA表达谱、miRNA-靶标相互作用以及功能分析,构建功能性SVD长链非编码RNA(lncRNA)介导的ceRNA网络(LMCN)。我们使用超几何检验来评估miRNA的富集显著性,并获得了LMCN,其包含27个lncRNA、7229个mRNA以及28871个lncRNA-mRNA相互关系对。此外,利用共表达分析构建了一个由21个lncRNA、129个mRNA和141个相互作用对组成的竞争性内源RNA(ceRNA)相互作用网络。我们确定转移相关肺腺癌转录本1和MIR155宿主基因在竞争性LMCN的一个网络模块中协同作用以调节mRNA。此外,通过基因本体论富集获得了7个基因。另外,通过Fisher检验获得了29条与lncRNA显著相关的mRNA富集通路。总之,我们鉴定出了7个与SVD相关的潜在lncRNA以及29条可能的lncRNA介导的通路。因此,ceRNA可以加速SVD中生物标志物的发现和治疗方法的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c370/5995035/dd5eb5d44922/etm-16-01-0121-g02.jpg

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