Integrative analysis of competing endogenous RNA networks reveals the functional lncRNAs in heart failure.
Integrative analysis of competing endogenous RNA networks reveals the functional lncRNAs in heart failure.
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DOI：
10.1111/jcmm.13739
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发表时间：
2018-10
影响因子：
5.3
通讯作者：
Tan X
中科院分区：
文献类型：
--
作者：
Fan Z;Gao S;Chen Y;Xu B;Yu C;Yue M;Tan X
心力衰竭已成为全球最主要的死亡原因之一。越来越多的证据表明，lncRNAs在多种心血管疾病的病理过程中发挥着重要作用。此外，lncRNAs还可以通过海绵化miRNAs来影响mRNAs的表达水平，从而发挥ceRNAs的作用，参与许多生物学过程。然而，lncRNAs在心力衰竭中的功能作用和调控机制仍不清楚。在我们的研究中，我们通过整合探针重新注释管道和miRNA-靶相互作用构建了一个与心力衰竭相关的lncRNA-mRNA网络。首先，在心力衰竭相关的LncRNA-mRNA网络中发现了一些具有中央拓扑特征的LncRNA。然后，使用双向层次聚类从网络中识别出与lncRNA相关的功能模块。一些参与模块的lncRNAs被证明在许多与心力衰竭相关的途径中都富含。为了研究lncRNA相关的Cerna串扰在某些疾病或生理状态中的作用，我们进一步鉴定了与lncRNA相关的失调的Cerna相互作用。我们还执行了随机行走算法来识别更多与心力衰竭相关的LncRNA。所有这些lncRNA都被证实对心力衰竭具有很强的诊断能力。这些结果将有助于我们理解lncRNAs在心力衰竭中的作用机制，并提供新的lncRNAs作为候选诊断生物标记物或潜在的治疗靶点。
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.
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