Kang Sheng, Ye Yong, Xia Guang, Liu Hai-Bo
Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai, China.
Department of Cardiology, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
Ann Transl Med. 2021 Feb;9(3):229. doi: 10.21037/atm-20-3487.
Previous studies have demonstrated associations between cardiovascular disease and the expression of various messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). This study aimed to investigate the differential expression of mRNAs, lncRNAs, and miRNAs between tissues from patients with coronary artery disease (CAD) and healthy controls, and to determine the interactions between these molecules in CAD.
We investigated the differential expression of competitive endogenous RNAs (ceRNAs) between patients with CAD and healthy controls by collecting data from Gene Expression Omnibus (GEO) microarrays. We also investigated the biological function of these differentially expressed ceRNAs by performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. We then created a protein-protein interaction (PPI) network to identify the hub genes. Biosystems and literature searches were also carried out to identify relevant signaling pathways and the potential function of the differentially expressed ceRNAs.
We identified 456 expression profiles for miRNAs, 16,325 mRNA expression profiles, and 2,869 lncRNA expression profiles. With regards to connectivity, GO and KEGG analyses (count ≥9) identified the top 11 PPI network nodes in rank order. We also identified the top 15 significant nodes for the ceRNAs identified according to degree centrality (DC) (P<0.05). Collectively, our analyses confirmed that the differential expression of certain ceRNAs, and their respective signaling pathways were associated with CAD.
Data arising from 11 GO and KEGG pathways, the top 15 PPI network nodes with the best connectivity rank, and the top 15 ceRNA network nodes, as determined by DC rank in CAD population, indicated that the differential expression of these ceRNAs plays a key role in the CAD. Our findings highlight new molecular mechanisms for CAD and provide new options for the development of therapeutic targets.
先前的研究已证明心血管疾病与各种信使核糖核酸（mRNA）、微小核糖核酸（miRNA）和长链非编码核糖核酸（lncRNA）的表达之间存在关联。本研究旨在调查冠心病（CAD）患者组织与健康对照组织之间mRNA、lncRNA和miRNA的差异表达，并确定这些分子在CAD中的相互作用。
我们通过从基因表达综合数据库（GEO）微阵列收集数据，研究CAD患者与健康对照之间竞争性内源性RNA（ceRNA）的差异表达。我们还通过进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，研究这些差异表达的ceRNA的生物学功能。然后我们创建了一个蛋白质-蛋白质相互作用（PPI）网络来识别枢纽基因。还进行了生物系统和文献检索，以识别相关信号通路以及差异表达的ceRNA的潜在功能。
我们鉴定出456个miRNA表达谱、16325个mRNA表达谱和2869个lncRNA表达谱。关于连通性，GO和KEGG分析（计数≥9）按排名顺序确定了前11个PPI网络节点。我们还根据度中心性（DC）（P<0.05）确定了ceRNA的前15个显著节点。总体而言，我们的分析证实某些ceRNA的差异表达及其各自的信号通路与CAD相关。
来自11条GO和KEGG通路的数据、CAD人群中连通性排名最佳的前15个PPI网络节点以及由DC排名确定的前15个ceRNA网络节点表明，这些ceRNA的差异表达在CAD中起关键作用。我们的研究结果突出了CAD的新分子机制，并为治疗靶点的开发提供了新的选择。
