Comparative characterization of microRNAs of Schistosoma japonicum from SCID mice and BALB/c mice: Clues to the regulation of parasite growth and development

Abstract

Schistosomiasis, caused by a parasite with a wide range of mammalian hosts, remains one of the most prevailing parasitic diseases in the world. While numerous studies have reported that the growth and reproduction of schistosomes in immunodeficient mice was significantly retarded, the underlying molecular mechanisms have yet to be revealed. In this study, we comparatively analyzed the microRNA expression of Schistosoma japonicum derived from SCID and BALB/c mice on the 35th day post-infection by high-throughput RNA sequencing as prominent morphological abnormalities had been observed in schistosomes from SCID mice when compared with those from BALB/c mice. The results revealed that more than 72% and 61% of clean reads in the small RNA libraries of female and male schistosomes, respectively, could be mapped to the selected miRs in the miRBase or the sequences of species-specific genomes. Further analysis identified 122 miRNAs using TPM >0.01 as the threshold value, including 75 known and 47 novel miRNAs, 96 of which were commonly expressed across all the four tested schistosome libraries. Comparative analysis of the libraries of schistosomes from SCID and BALB/c mice identified 15 differentially expressed miRNAs (5 up-regulated and 10 down-regulated) among females and 16 among males (9 up-regulated and 7 down-regulated). Integrated analysis of the two sets of differentially expressed miRNAs of female and male worms identified 2 miRNAs (sja-miR-3488 and sja-miR-novel_29) that overlapped between female and male datasets. Prediction of miRNA targets and Gene Ontology (GO) term enrichment analysis of the predicted target genes revealed that these genes were involved in some important biological processes, such as nucleic acid metabolic process, macromolecule modification, and cellular aromatic compound metabolic process. The predicted target genes were further matched to the differentially expressed genes in male and female schistosomes from the above two hosts, obtaining 7 genes that may be responsible for regulating the growth, development and sex maturation of schistosomes. Taken together, this study provides the first identification of differentially expressed miRNAs in schistosomes from SCID and BALB/c mice. These miRNAs and their predicted target mRNAs are probably involved in the regulation of development, growth, and maturation of schistosomes. Therefore, this study expands our understanding of schistosome development regulation and host-parasite relationship, and also provides a valuable set of potential anti-schistosomal targets for prevention and control of schistosomiasis.