Objectives: Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) remain the major pathogens in hand, foot, and mouth disease (HFMD) cases, but the mechanisms of the different pathogeneses that follow EV71 and CA16 infection remain largely unknown. Methods: Herein, we utilized microRNA (miRNA) deep sequencing to investigate the roles of novel differentially expressed miRNAs in peripheral blood mononuclear cells (PBMCs) infected with EV71 and CA16. Results: The results identified 13 novel differentially expressed miRNAs in each group. Additionally, the target genes were predicted by the miRanda and RNAhybrid programs, and a total of 2,501 targets were found in the two databases. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these targets were mainly involved in cell development and were associated with nervous system development, system development, multicellular organism development, the Wnt signaling pathway, the PDGF signaling pathway, and the EGF receptor signaling pathway. Finally, a coexpression regulatory network was built with the key targets to further extrapolate the functional interactions of the targets and their coexpressed genes. Conclusion: Our results not only revealed potential biomarkers or targets for the diagnosis and treatment of HFMD, but also provided new insights to explore the mechanisms of EV71 and CA16 pathogenesis.
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