sja-miR-2a-3p is Associated with Apoptosis-Related Responses in Schistosoma japonicum.

PURPOSE: Schistosoma japonicum develops efficiently in BALB/c mice but poorly in less-permissive Wistar rats. Previous studies showed that parasites from Wistar rats display higher apoptotic activity, while sja-miR-2a-3p is more highly expressed in Wistar rat-derived schistosomula. This study examined whether sja-miR-2a-3p is associated with apoptosis-related responses in S. japonicum. METHODS: Published small RNA-seq datasets were reanalyzed to assess sja-miR-2a-3p expression during worm development and in schistosomula from BALB/c mice and Wistar rats. Regional expression of sja-miR-2a-3p was examined in dissected male and female worms. Predicted targets were subjected to enrichment analysis. Adult paired worms were cultured in vitro and treated with sja-miR-2a-3p mimics, inhibitor, or corresponding negative controls. miRNA expression, egg output, apoptosis-related gene expression and TUNEL signals were evaluated. RESULTS: sja-miR-2a-3p was expressed from 14 to 28 days post infection and was higher in Wistar rat-derived schistosomula than in BALB/c mouse-derived schistosomula. In adult worms, sja-miR-2a-3p was enriched in the male testis/posterior region and female vitellaria. Target enrichment suggested involvement in stimulus response, growth, biological regulation, homeostasis and signaling pathways. Mimic treatment increased sja-miR-2a-3p levels and upregulated multiple apoptosis-associated genes, including sjaAIF, sjaAPAF, sjaBAX, sjaCASP3, sjaCASP9, sjaCYC and sjaTNFR. TUNEL staining further showed increased apoptotic signals after sja-miR-2a-3p overexpression. CONCLUSION: sja-miR-2a-3p is a tissue-biased miRNA linked to apoptosis-related responses in S. japonicum. These findings suggest that elevated sja-miR-2a-3p may contribute to the increased apoptotic state of parasites developing in less-permissive hosts.