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慢性阻塞性肺疾病急性加重期患者肌肉力量丧失相关关键基因和微小RNA的预测

Prediction of key genes and miRNAs responsible for loss of muscle force in patients during an acute exacerbation of chronic obstructive pulmonary disease.

作者信息

Duan Yanhong, Zhou Min, Xiao Jian, Wu Chaomin, Zhou Lei, Zhou Feng, Du Chunling, Song Yuanlin

机构信息

Department of Respiratory Medicine, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, P.R. China.

Department of Respiratory Medicine, Jinshan Branch of The Sixth People's Hospital of Shanghai, Shanghai 201599, P.R. China.

出版信息

Int J Mol Med. 2016 Nov;38(5):1450-1462. doi: 10.3892/ijmm.2016.2761. Epub 2016 Sep 30.

Abstract

The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD. Differentially expressed genes (DEGs) were screened using the Limma package in R. A protein‑protein interaction (PPI) network of DEGs was built based on the STRING database. Module analysis of the PPI network was performed using the ClusterONE plugin and functional analysis of DEGs was conducted using DAVID. Additionally, key miRNAs were enriched using gene set enrichment analysis (GSEA) software and a miR-gene regulatory network was constructed using Cytoscape software. In total, 166 up- and 129 downregulated DEGs associated with muscle weakness in AECOPD were screened. Among them, NCL, GOT1, TMOD1, TSPO, SOD2, NCL and PA2G4 were observed in the modules consisting of upregulated or downregulated genes. The upregulated DEGs in modules (including KLF6 and XRCC5) were enriched in GO terms associated with immune system development, whereas the downregulated DEGs were enriched in GO terms associated with cell death and muscle contraction. Additionally, 39 key AECOPD‑related miRNAs were also predicted, including miR-1, miR-9 and miR-23a, miR-16 and miR-15a. In conclusion, DEGs (NCL, GOT1, SOD2, KLF6, XRCC5, TSPO and TMOD1) and miRNAs (such as miR-1, miR-9 and miR-23a) may be associated with the loss of muscle force in patients during an acute exacerbation of COPD which also may act as therapeutic targets in the treatment of AECOPD.

摘要

本研究旨在鉴定在慢性阻塞性肺疾病急性加重期(AECOPD)患者的股外侧肌中异常表达的基因和微小RNA(miRNA或miR)。从基因表达综合数据库下载了GSE10828的基因表达谱,该数据集由4个AECOPD患者的样本和5个稳定期慢性阻塞性肺疾病患者的样本组成。使用R语言中的Limma软件包筛选差异表达基因(DEG)。基于STRING数据库构建DEG的蛋白质-蛋白质相互作用(PPI)网络。使用ClusterONE插件对PPI网络进行模块分析,并使用DAVID对DEG进行功能分析。此外,使用基因集富集分析(GSEA)软件富集关键miRNA,并使用Cytoscape软件构建miR-基因调控网络。总共筛选出166个上调和129个下调的与AECOPD肌肉无力相关的DEG。其中,NCL、GOT1、TMOD1、TSPO、SOD2、NCL和PA2G4出现在由上调或下调基因组成的模块中。模块中的上调DEG(包括KLF6和XRCC5)在与免疫系统发育相关的基因本体(GO)术语中富集,而下调的DEG在与细胞死亡和肌肉收缩相关的GO术语中富集。此外,还预测了39个与AECOPD相关的关键miRNA,包括miR-1、miR-9和miR-23a、miR-16和miR-15a。总之,DEG(NCL、GOT1、SOD2、KLF6、XRCC5、TSPO和TMOD1)和miRNA(如miR-1、miR-9和miR-23a)可能与COPD急性加重期患者的肌肉力量丧失有关,它们也可能成为AECOPD治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e72/5065306/aa356f1b19ee/IJMM-38-05-1450-g00.jpg

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