Long noncoding RNAs (lncRNAs) have been increasingly accepted to function importantly in human diseases by serving as competing endogenous RNAs (ceRNAs). To date, the ceRNA mechanisms of lncRNAs in the progression of atherosclerosis (AS) remain largely unclear. On the basis of ceRNA theory, we implemented a multistep computational analysis to construct an lncRNA–mRNA network for AS progression (ASpLMN). The probe reannotation method and microRNA–target interactions from databases were systematically integrated. Three lncRNAs (GS1-358P8.4, OIP5-AS1, and TUG1) with central topological features in the ASpLMN were firstly identified. By using subnetwork analysis, we then obtained two highly clustered modules and one dysregulated module from the ASpLMN network. These modules, sharing three lncRNAs (GS1-358P8.4, OIP5-AS1, and RP11-690D19.3), were significantly enriched in biological pathways such as regulation of actin cytoskeleton, tryptophan metabolism, lysosome, and arginine and proline metabolism. In addition, random walking in the ASpLMN network indicated that lncRNA RP1-39G22.7 and MBNL1-AS1 may also play an essential role in the pathology of AS progression. The identified six lncRNAs from the aforementioned steps could distinguish advanced- from early-staged AS, with a strong diagnostic power for AS occurrence. In conclusion, the results of this study will improve our understanding about the ceRNA-mediated regulatory mechanisms in AS progression, and provide novel lncRNAs as biomarkers or therapeutic targets for acute cardiovascular events.

中文翻译：

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长的非编码RNA在动脉粥样硬化的进展：基于竞争内源RNA理论的综合分析。

长非编码RNA（lncRNA）被用作竞争性内源RNA（ceRNA），在人类疾病中起重要作用。迄今为止，在动脉粥样硬化（AS）进程中，lncRNA的ceRNA机制尚不清楚。在ceRNA理论的基础上，我们实施了多步计算分析，以构建用于AS进展（ASpLMN）的lncRNA–mRNA网络。系统整合了探针重新注释方法和数据库中的microRNA-靶标相互作用。三个lncRNA（GS1-358P8.4，OIP5-AS1和TUG1最早在ASpLMN中具有中心拓扑特征。通过使用子网分析，我们然后从ASpLMN网络获得了两个高度聚类的模块和一个失调的模块。这些模块，共享三个lncRNA（GS1-358P8.4，OIP5-AS1和RP11-690D19.3），在诸如调节肌动蛋白细胞骨架，色氨酸代谢，溶酶体，精氨酸和脯氨酸代谢等生物学途径中显着丰富。此外，在ASpLMN网络中随机行走表明lncRNA RP1-39G22.7和MBNL1-AS1在AS进展的病理过程中也可能起重要作用。从上述步骤中鉴定出的六个lncRNA可以区分晚期AS和早期AS，对AS发生具有强大的诊断能力。总之，这项研究的结果将增进我们对AS进展中ceRNA介导的调控机制的了解，并提供新颖的lncRNA作为急性心血管事件的生物标记或治疗靶标。