Shi Hongbo, Zhang Guangde, Wang Jing, Wang Zhenzhen, Liu Xiaoxia, Cheng Liang, Li Weimin
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, 150081, PR China.
Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, PR China.
PLoS One. 2016 Jul 1;11(7):e0158638. doi: 10.1371/journal.pone.0158638. eCollection 2016.
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.
心肌梗死(MI)是一种严重的心脏病,也是全球范围内导致死亡和发病的主要原因。尽管一些与MI相关的分子(基因、微小RNA(miRNA)和转录因子(TF))已在特定病理背景下进行了研究,但它们在MI进展过程中的基因表达、生物学功能和调控相互作用的动态特征迄今尚未完全阐明。在本研究中,我们分析了外周血单核细胞的时间序列RNA表达数据。我们观察到,在MI急性期,显著差异表达的基因急剧上调或下调,然后缓慢变化直至慢性期。确定了MI各阶段涉及的生物学功能。此外,基于显著差异表达的基因和miRNA-TF共调控基序构建了动态miRNA-TF共调控网络,并研究了miRNA、TF和靶基因之间的动态相互作用。最后,鉴定出一组新的候选诊断生物标志物(信号转导和转录激活因子3(STAT3)和细胞间黏附分子1(ICAM1))对有无MI的患者,尤其是有无复发事件的患者具有鉴别能力。本研究结果不仅为理解MI进展所涉及的潜在调控机制提供了新的线索,也有助于发现MI真正的诊断生物标志物。