Construction of miRNA-target networks using microRNA profiles of CVB3-infected HeLa cells.

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.