Different microRNA profiles reveal the diverse outcomes induced by EV71 and CA16 infection in human umbilical vein endothelial cells using high-throughput sequencing.
Different microRNA profiles reveal the diverse outcomes induced by EV71 and CA16 infection in human umbilical vein endothelial cells using high-throughput sequencing.
复制标题
使用高通量测序，不同的 microRNA 图谱揭示了 EV71 和 CA16 感染人脐静脉内皮细胞诱导的不同结果
DOI：
10.1371/journal.pone.0177657
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Song J;Hu Y;Li J;Zheng H;Wang J;Guo L;Ning R;Li H;Yang Z;Fan H;Liu L
肠道病毒71型(EV71)和柯萨奇病毒A16(CA16)仍然是手足口病(HFMD)的主要病原体，但EV71和CA16感染的致病因素尚未阐明。近年来，microRNAs(MiRNAs)在病原菌-宿主相互作用中的作用受到重视。在本研究中，我们使用高通量测序技术在多个时间点对EV71和CA16感染的人脐静脉内皮细胞(HUVECs)进行了全面的miRNA图谱分析。结果表明，已知的135个miRNAs在表达上存在显著差异。其中，30个差异表达的miRNAs在EV71和CA16感染的样本中表现出相反的趋势。随后，我们通过进一步的筛选，主要针对30个关键的差异表达miRNAs进行靶点预测。预测靶点的基因本体(GO)和通径分析表明，14个生物学过程、9个分子功能、8个细胞成分和85条途径得到了丰富。确定了这些miRNAs与预测的靶标、GO、途径和共表达基因的调控网络，表明miRNAs在感染阶段表现出复杂的调控机制。因此，我们具体分析了生物黏附所涉及的预测目标的GO分级类别。结果表明，EV71和CA16感染引起的明显变化可能与血脑屏障的功能有关。综上所述，这是第一份使用高通量测序描述EV71和CA16感染的HUVEC中miRNA表达谱的报告。我们的数据提供了有用的见解，可能有助于阐明EV71和CA16感染后不同的宿主-病原体相互作用，并为这些感染提供新的治疗靶点。
Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) remain the predominant pathogens in hand, foot, and mouth disease (HFMD), but the factors underlying the pathogenesis of EV71 and CA16 infections have not been elucidated. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. In the present study, we performed comprehensive miRNA profiling in EV71- and CA16-infected human umbilical vein endothelial cells (HUVECs) at multiple time points using high-throughput sequencing. The results showed that 135 known miRNAs exhibited remarkable differences in expression. Of these, 30 differentially expressed miRNAs presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 30 key differentially expressed miRNAs through further screening to predict targets. Gene ontology (GO) and pathway analysis of the predicted targets showed the enrichment of 14 biological processes, 9 molecular functions, 8 cellular components, and 85 pathways. The regulatory networks of these miRNAs with predicted targets, GOs, pathways, and co-expression genes were determined, suggesting that miRNAs display intricate regulatory mechanisms during the infection phase. Consequently, we specifically analyzed the hierarchical GO categories of the predicted targets involved in biological adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to the function of the blood-brain barrier. Taken together, this is the first report describing miRNA expression profiles in HUVECs with EV71 and CA16 infections using high-throughput sequencing. Our data provide useful insights that may help to elucidate the different host-pathogen interactions following EV71 and CA16 infection and offer novel therapeutic targets for these infections.