Zhang Guangde, Sun Haoran, Zhang Yawei, Zhao Hengqiang, Fan Wenjing, Li Jianfei, Lv Yingli, Song Qiong, Li Jiayao, Zhang Mingyu, Shi Hongbo
1Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, 150001 Harbin, Heilongjiang China.
2College of Bioinformatics Science and Technology, Harbin Medical University, 150081 Harbin, Heilongjiang China.
Cell Death Discov. 2018 Feb 21;4:35. doi: 10.1038/s41420-018-0036-7. eCollection 2018 Dec.
Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on "ceRNA hypothesis". We systematically integrated lncRNA and mRNA expression profiles and miRNA-target regulatory interactions. The constructed DLMN_MI_OC and DLMN_MI_Re both exhibited biological network characteristics, and functional analysis demonstrated that the networks were specific for MI. Additionally, we identified some lncRNA-mRNA ceRNA modules involved in MI occurrence and recurrence. Finally, two new panel biomarkers defined by four lncRNAs (, , , ) from DLMN_MI_OC and three lncRNAs (, , ) from DLMN_MI_Re with high classification performance were, respectively, identified in distinguishing controls from patients, and patients with recurrent events from those without recurrent events. This study will provide us new insight into ceRNA-mediated regulatory mechanisms involved in MI occurrence and recurrence, and facilitate the discovery of candidate diagnostic and prognosis biomarkers for MI.
越来越多的证据表明，作为竞争性内源RNA（ceRNA）的长链非编码RNA（lncRNA）在人类疾病的发生和发展中发挥着重要作用。然而，lncRNA调控的ceRNA在心肌梗死（MI）中的机制仍不清楚。在本研究中，我们基于“ceRNA假说”，采用多步骤计算方法构建了用于MI发生（DLMN_MI_OC）和复发（DLMN_MI_Re）的失调lncRNA- mRNA网络。我们系统地整合了lncRNA和mRNA表达谱以及miRNA-靶标调控相互作用。构建的DLMN_MI_OC和DLMN_MI_Re均表现出生物网络特征，功能分析表明这些网络对MI具有特异性。此外，我们鉴定了一些参与MI发生和复发的lncRNA- mRNA ceRNA模块。最后，分别从DLMN_MI_OC中的四个lncRNA（、、、）和DLMN_MI_Re中的三个lncRNA（、、）定义的两个具有高分类性能的新的生物标志物面板，在区分对照组与患者以及复发事件患者与无复发事件患者方面得到了鉴定。本研究将为我们提供关于ceRNA介导的参与MI发生和复发的调控机制的新见解，并促进MI候选诊断和预后生物标志物的发现。
