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Integrative analysis of competing endogenous RNA networks reveals the functional lncRNAs in heart failure
Authors:Zhimin Fan  Shanshan Gao  Yequn Chen  Bayi Xu  Chengzhi Yu  Minghui Yue  Xuerui Tan
Affiliation:1. Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China;2. Shantou University Medical College, Shantou, Guangdong, China
Abstract:Heart failure has become one of the top causes of death worldwide. It is increasing evidence that lncRNAs play important roles in the pathology processes of multiple cardiovascular diseases. Additionally, lncRNAs can function as ceRNAs by sponging miRNAs to affect the expression level of mRNAs, implicating in numerous biological processes. However, the functional roles and regulatory mechanisms of lncRNAs in heart failure are still unclear. In our study, we constructed a heart failure‐related lncRNA‐mRNA network by integrating probe re‐annotation pipeline and miRNA‐target interactions. Firstly, some lncRNAs that had the central topological features were found in the heart failure‐related lncRNA‐mRNA network. Then, the lncRNA‐associated functional modules were identified from the network, using bidirectional hierarchical clustering. Some lncRNAs that involved in modules were demonstrated to be enriched in many heart failure‐related pathways. To investigate the role of lncRNA‐associated ceRNA crosstalks in certain disease or physiological status, we further identified the lncRNA‐associated dysregulated ceRNA interactions. And we also performed a random walk algorithm to identify more heart failure‐related lncRNAs. All these lncRNAs were verified to show a strong diagnosis power for heart failure. These results will help us to understand the mechanism of lncRNAs in heart failure and provide novel lncRNAs as candidate diagnostic biomarkers or potential therapeutic targets.
Keywords:biological network  ceRNA  dysregulated ceRNA  heart failure  lncRNA
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