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首页> 美国卫生研究院文献>other >Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells
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Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells

机译：通过整合miRNA转录因子共调节网络和来自外周血单个核细胞的时间序列RNA表达数据研究心肌梗塞进展的动态特征

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摘要

Myocardial infarction (MI) is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs)) associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA–TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA–TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1) was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI.
机译：心肌梗塞（MI）是一种严重的心脏病，并且是全球范围内死亡率和发病率的主要原因。尽管已经在特定的病理学背景下研究了与MI相关的某些分子（基因，miRNA和转录因子（TF）），但迄今为止，尚未完全阐明其在MI进展中的基因表达，生物学功能和调节相互作用的动态特征。在本研究中，我们分析了来自外周血单个核细胞的时间序列RNA表达数据。我们观察到，显着差异表达的基因在MI的急性期急剧上调或下调，然后缓慢变化直至慢性期。确定了MI各个阶段涉及的生物学功能。此外，基于显着差异表达的基因和miRNA-TF共同调控基序，构建了动态miRNA-TF共同调控网络，并研究了miRNA，TF和靶基因的动态相互作用。最后，鉴定出一组新的候选诊断生物标记物（STAT3和ICAM1），对有或没有MI的患者，特别是有或没有复发事件的患者具有区分能力。本研究的结果不仅为了解与MI进展有关的调控机制提供了新的思路，而且为发现MI的真正诊断生物标志物做出了贡献。

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