Profiling of Novel MicroRNAs Elicited by EV71 and CA16 Infection in Human Bronchial Epithelial Cells Using High-throughput Sequencing

Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are two major etiologic agents associated with hand, foot, and mouth disease (HFMD) worldwide. Despite that they both belong to the Enterovirus genus of the Picornaviridae family, there are many differences in the infection process of these viruses. However, the underlying mechanisms have not been elucidated. Multiple studies indicated that microRNAs (miRNAs) can play critical roles in the host-pathogen interaction. Our previous study reported that EV71 and CA16 infection leads to differential expression of miRNAs in human bronchial epithelial (16HBE) cells. Herein, we aimed to further explore the expression profile and possible roles of other differentially expressed miRNAs in 16HBE cells following EV71 and CA16 infections using high-throughput sequencing. We describe 44 novel differentially expressed miRNAs in all samples. Among these miRNAs, 7 novel differentially expressed miRNAs show an opposite expression trend during the progression of EV71 and CA16 infections. Subsequently, bioinformatics analyses, including Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were used to identify the biological processes, molecular functions, cellular components, and pathways involved. The top 10 significant GO and Pathway annotations indicated that 849 target genes are involved in cell development, such as nervous system development, multicellular organism development, and developmental biology. Finally, the genes identified in both the GO and Pathway analysis were used to construct a co-expression network to further identify the potential function of these co-expressed genes. Thus, our data may be beneficial in guiding further studies on the molecular mechanism of developmental regulation in HFMD pathogenesis caused by EV71 and CA16. In addition, it provided new candidate biomarkers or therapeutic targets for HFMD.