Department of Biochemistry & Immunology, Capital Institute of Pediatrics, 2 YaBao Rd, Beijing, 100020, China.
State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing, 102206, China.
Sci Rep. 2019 Nov 29;9(1):17876. doi: 10.1038/s41598-019-54188-w.
MicroRNAs (miRNAs) play an important role in regulating gene expression in multiple biological processes and diseases. Thus, to understand changes in miRNA during CVB3 infection, specific miRNA expression profiles were investigated at 3 h, 6 h, and 9 h postinfection in HeLa cells by small-RNA high-throughput sequencing. Biological implications of 68 differentially expressed miRNAs were analyzed through GO and KEGG pathways. Interaction networks between 34 known highly differentially expressed miRNAs and targets were constructed by mirDIP and Navigator. The predicted targets showed that FAM135A, IKZF2, PLAG1, ZNF148, PHC3, LCOR and DYRK1A, which are associated with cellular differentiation and transcriptional regulation, were recognized by 8 miRNAs or 9 miRNAs through interactional regulatory networks. Seven target genes were confirmed by RT-qPCR. The results showed that the expression of DYRK1A, FAM135A, PLAG1, ZNF148, and PHC3 were obviously inhibited at 3 h, 6 h, and 9 h postinfection. The expression of LCOR did not show a significant change, and the expression of IKZF2 increased gradually with prolonged infection time. Our findings improve the understanding of the pathogenic mechanism of CVB3 infection on cellular differentiation and development through miRNA regulation, which has implications for interventional approaches to CVB3-infection therapy. Our results also provide a new method for screening target genes of microRNA regulation in virus-infected cells.
微小 RNA（miRNAs）在多个生物过程和疾病的基因表达调控中发挥着重要作用。因此，为了了解 CVB3 感染过程中 miRNA 的变化，本研究通过小 RNA 高通量测序，在感染后 3 h、6 h 和 9 h 时检测 HeLa 细胞中特定的 miRNA 表达谱。通过 GO 和 KEGG 途径分析了 68 个差异表达 miRNA 的生物学意义。通过 mirDIP 和 Navigator 构建了 34 个已知高度差异表达 miRNA 和靶基因之间的相互作用网络。预测的靶基因表明，FAM135A、IKZF2、PLAG1、ZNF148、PHC3、LCOR 和 DYRK1A 与细胞分化和转录调控有关，通过相互作用的调控网络，8 个 miRNA 或 9 个 miRNA 可以识别 FAM135A、IKZF2、PLAG1、ZNF148、PHC3、LCOR 和 DYRK1A。通过 RT-qPCR 验证了 7 个靶基因。结果表明，DYRK1A、FAM135A、PLAG1、ZNF148 和 PHC3 的表达在感染后 3 h、6 h 和 9 h 时明显受到抑制。LCOR 的表达没有明显变化，而 IKZF2 的表达随着感染时间的延长而逐渐增加。本研究结果通过 miRNA 调控改善了对 CVB3 感染对细胞分化和发育的致病机制的认识，这对 CVB3 感染治疗的干预方法具有重要意义。本研究结果还为筛选病毒感染细胞中 miRNA 调控的靶基因提供了一种新方法。
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