MiR-342-5p targets CTNNBIP1 to promote enterovirus 71 replication

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ObjectiveThe aim of this research was to explore the role of miR-342-5p in EV71 replication. MethodsPeritoneal injection of EV71 (107 TCID50/mL) at 50, 100, and 150 μL was conducted to infect 12-day-old suckling mice (n = 10 per group), and clinical scores and survival rates were recorded during a 6-day trial duration and followed by transcriptome sequencing of collected spinal cord tissues. The differential miRNAs and target genes of the infected and uninfected EV71 mice were analyzed. The miR-342 and CTNNBIP1 binding sites were detected using a dual luciferase reporter assay. Cell viability was detected by CCK-8. RT-qPCR, Western blot, immunofluorescence, and immunohistochemistry assays were conducted to detect VP1 protein levels. ResultsTranscriptome sequencing analyses know that the Wnt pathway played a role in EV71 infection, and the CTNNBIP1 gene in this pathway was the target gene of miR-342-5p. Whether in HMC3 cells or in the spinal cord tissue from the suckling mice, high levels of miR-342-5p markedly promoted EV71 VP1 mRNA and protein expression, elevated TNF-α, IL-6, and IL-10 levels, and inhibited IFN-β levels. In addition, highly expressed miR-342-5p destroyed neuronal structure in spinal cord tissues and reduced the number of glial cells. Highly expressed CTNNBIP1 blocked the promotion of miR-342-5p in EV71 replication, and inhibited TNF-α, IL-6, and IL-10 levels, whereas elevated IFN-β levels. This mechanism is that miR-342-5p can target the CTNNBIP1 3’ UTR region, inhibit its expression and reduce its binding to CTNNB1, thus enhancing the interaction between CTNNB1 and TCF4 and activating the Wnt pathway-mediated type I interferon response. ConclusionIn nerve cells and tissues, the overexpression of miR-342-5p promoted the replication of EV71 and attenuated the innate immune response to antiviral disease via Wnt/CTNNB1 signaling pathway.