Ji Yuyao, Yan Tao, Zhu Shijie, Wu Runda, Zhu Miao, Zhang Yangyang, Guo Changfa, Yao Kang
Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Cardiovasc Med. 2021 Sep 22;8:647953. doi: 10.3389/fcvm.2021.647953. eCollection 2021.
Coronary artery disease (CAD) is the leading cause of cardiovascular death. The competitive endogenous RNAs (ceRNAs) hypothesis is a new theory that explains the relationship between lncRNAs and miRNAs. The mechanism of ceRNAs in the pathological process of CAD has not been fully elucidated. The objective of this study was to explore the ceRNA mechanism in CAD using the integrative bioinformatics analysis and provide new research ideas for the occurrence and development of CAD. The GSE113079 dataset was downloaded, and differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) were identified using the limma package in the R language. Weighted gene correlation network analysis (WGCNA) was performed on DElncRNAs and DEGs to explore lncRNAs and genes associated with CAD. Functional enrichment analysis was performed on hub genes in the significant module identified WGCNA. Four online databases, including TargetScan, miRDB, miRTarBase, and Starbase, combined with an online tool, miRWalk, were used to construct ceRNA regulatory networks. DEGs were clustered into ten co-expression modules with different colors using WGCNA. The brown module was identified as the key module with the highest correlation coefficient. 188 hub genes were identified in the brown module for functional enrichment analysis. DElncRNAs were clustered into sixteen modules, including seven modules related to CAD with the correlation coefficient more than 0.5. Three ceRNA networks were identified, including OIP5-AS1-miR-204-5p/miR-211-5p-SMOC1, OIP5-AS1-miR-92b-3p-DKK3, and OIP5-AS1-miR-25-3p-TMEM184B. Three ceRNA regulatory networks identified in this study may play crucial roles in the occurrence and development of CAD, which provide novel insights into the ceRNA mechanism in CAD.
冠状动脉疾病（CAD）是心血管死亡的主要原因。竞争性内源性RNA（ceRNA）假说为解释长链非编码RNA（lncRNA）与微小RNA（miRNA）之间的关系提供了新理论。ceRNA在CAD病理过程中的机制尚未完全阐明。本研究旨在通过综合生物信息学分析探索CAD中的ceRNA机制，为CAD的发生发展提供新的研究思路。下载了GSE113079数据集，并使用R语言中的limma软件包鉴定差异表达的lncRNA（DElncRNA）和基因（DEG）。对DElncRNA和DEG进行加权基因共表达网络分析（WGCNA），以探索与CAD相关的lncRNA和基因。对WGCNA鉴定出的显著模块中的枢纽基因进行功能富集分析。利用包括TargetScan、miRDB、miRTarBase和Starbase在内的四个在线数据库，并结合在线工具miRWalk构建ceRNA调控网络。使用WGCNA将DEG聚类为十个具有不同颜色的共表达模块。棕色模块被确定为相关系数最高的关键模块。在棕色模块中鉴定出188个枢纽基因进行功能富集分析。DElncRNA被聚类为16个模块，其中包括7个与CAD相关且相关系数大于0.5的模块。鉴定出三个ceRNA网络，包括OIP5-AS1-miR-204-5p/miR-211-5p-SMOC1、OIP5-AS1-miR-92b-3p-DKK3和OIP5-AS1-miR-25-3p-TMEM184B。本研究鉴定出的三个ceRNA调控网络可能在CAD的发生发展中起关键作用，这为CAD中的ceRNA机制提供了新见解。
