Comprehensive Construction of a Circular RNA-Associated Competing Endogenous RNA Network Identified Novel Circular RNAs in Hypertrophic Cardiomyopathy by Integrated Analysis
Comprehensive Construction of a Circular RNA-Associated Competing Endogenous RNA Network Identified Novel Circular RNAs in Hypertrophic Cardiomyopathy by Integrated Analysis
复制标题
全面构建环状RNA相关竞争性内源RNA网络，通过综合分析鉴定出肥厚型心肌病中的新型环状RNA
DOI：
10.3389/fgene.2020.00764
复制
发表时间：
2020-07-28
影响因子：
3.7
通讯作者：
Zhang, Yuling
中科院分区：
文献类型：
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作者：
Guo, Qi;Wang, Junjie;Zhang, Yuling
肥厚型心肌病（HCM）是最常见的遗传性心肌病，与心脏性猝死的高风险相关。HCM中环状RNA（circRNA）相关的竞争性内源性RNA（ceRNA）网络的复杂性和行为尚未完全阐明。通过使用微阵列获得血浆circRNA和信使RNA（mRNA）表达谱。采用加权相关网络分析（WGCNA）和微阵列数据线性模型（Limma）分析微阵列数据。检测由具有高相关性的基因组成的基因模块，并用指定的颜色表示。基于“ceRNA假说”，采用整合系统生物学方法构建了包括circRNA、microRNA（miRNA）和mRNA的ceRNA网络。通过WGCNA，两个模块，即洋红色和红色模块，被确定为与HCM正相关。在WGCNA和Limma的联合分析中，与对照相比，洋红色模块中的36个枢纽circRNA和红色模块中的83个枢纽circRNA显著上调。通过共表达分析，鉴定了270个circRNA-mRNA对，相关系数>= 0.9和p < 0.05。使用Starbase和miRWalk工具预测circRNA-miRNA对和miRNA-mRNA对。一旦这些对被组合，就构建了具有6个circRNA、29个miRNA和6个mRNA的ceRNA网络。功能分析表明，ceRNA网络中的这些circRNA与钙释放通道活性和肌丝滑动相关。我们的研究为HCM中circRNA相关的ceRNA网络提供了全球视角和系统分析。鉴定的circRNA hsa_circ_0043762、hsa_circ_0036248和hsa_circ_0071269可能是参与HCM发病机制的关键调节因子。
Hypertrophic cardiomyopathy (HCM), the most common heritable cardiomyopathy, is associated with a high risk of sudden cardiac death. The complexity and behavior of the circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) network in HCM have not been thoroughly elucidated. Plasma circRNA and messenger RNA (mRNA) expression profiles were acquired by using a microarray. Weighted correlation network analysis (WGCNA) and linear models for microarray data (Limma) were used to analyze microarray data. Gene modules, consisting of genes with high correlations, were detected and represented by a designated color. The ceRNA network, including circRNA, microRNA (miRNA), and mRNA, was constructed based on the "ceRNA hypothesis" using an integrated systems biology method. By WGCNA, two modules, namely magenta and red modules, were identified as being positively correlated with HCM. In the combined analysis of WGCNA and Limma, 36 hub circRNAs in the magenta module and 83 hub circRNAs in the red module were significantly upregulated compared with the controls. By coexpression analysis, 270 circRNA-mRNA pairs were identified with a coefficient >= 0.9 andp< 0.05. With Starbase and miRWalk tools, circRNA-miRNA pairs and miRNA-mRNA pairs were predicted. Once these pairs were combined, the ceRNA network with 6 circRNAs, 29 miRNAs, and 6 mRNAs was constructed. Functional analysis demonstrated that these circRNAs in the ceRNA network were associated with calcium-release channel activity and muscle filament sliding. Our study provided a global perspective and systematic analysis of the circRNA-associated ceRNA network in HCM. The identified circRNAs hsa_circ_0043762, hsa_circ_0036248, and hsa_circ_0071269 may be key regulators involved in HCM pathogenesis.