MicroRNAs: potentially important regulators for schistosome development and therapeutic targets against schistosomiasis.
ABSTRACT MicroRNAs (miRNAs) are small, endogenous non-coding RNA molecules that regulate gene expression post-transcriptionally by targeting the 3' untranslated region (3' UTR) of messenger RNAs. Since the discovery of the first miRNA in Caenorhabditis elegans, important regulatory roles for miRNAs in many key biological processes including development, cell proliferation, cell differentiation and apoptosis of many organisms have been described. Hundreds of miRNAs have been identified in various multicellular organisms and many are evolutionarily conserved. Schistosomes are multi-cellular eukaryotes with a complex life-cycle that require genes to be expressed and regulated precisely. Recently, miRNAs have been identified in two major schistosome species, Schistosoma japonicum and S. mansoni. These miRNAs are likely to play critical roles in schistosome development and gene regulation. Here, we review recent studies on schistosome miRNAs and discuss the potential roles of miRNAs in schistosome development and gene regulation. We also summarize the current status for targeting miRNAs and the potential of this approach for therapy against schistosomiasis.
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ABSTRACT: Schistosoma japonicum is one of the major causative agents of schistosomiasis. The pairing of males and females leads to female sexual maturation and maintains this mature state. However, the mechanisms by which pairing facilitates sexual maturation are yet to be investigated. Parasites isolated from single- and double-sex cercariae-infected mice were analyzed by Solexa to uncover pair-regulated miRNA profiles. To reveal the biological functions of differentially expressed miRNAs among the samples, we predicted the target genes of these differentially expressed miRNAs and compared the gene expression between 23-d-old female schistosomula from double-sex infections (23DSI) and 23-d-old female schistosomula from single-sex infections (23SSI) by analyzing digital gene expression profiling (DGE). KEGG pathway analysis was used to investigate the relevant biological processes of these target genes to understand the significance of differentially expressed miRNAs after pairing. The differentially expressed miRNA profiles of female 18- and 23-d post-single- and double-sex infections were analysed by Solexa. Similar miRNA profiles were observed in 18SSI and 18DSI, with the presence of identically expressed high-abundance miRNA, such as miRNA-1, miRNA-71b-5p and let-7. By contrast, in 23DSI and 23SSI, most of these high-abundance miRNAs were down-regulated. Furthermore, among all samples, bantam was distinctly up-regulated in 23 DSI, and miR-1, miR-71, miR-7-5p, and miR-7 were distinctly up-regulated in 23SSI. The transcriptomes of 23DSI and 23SSI revealed that the predicted target genes of miRNA-1, miRNA-71, miRNA-7, and miR-7-5p were associated with the ribonucleoprotein complex assembly and microtubule-based process. Conversely, the predicted target genes of bantam were related to the embryo development, development of primary sexual characteristics and regulation of transcription. KEGG pathway analysis revealed that in unpaired females, the highly-expressed miRNA-1, miRNA-71, miRNA-7, and miR-7-5p only inhibited the limited pathways, such as proteasome and ribosome assembly. Meanwhile, in paired mature females, highly-expressed bantam inhibited more biological pathways, such as the citrate cycle, glycolysis, fatty acid biosynthesis and RNA degradation. The differentially expressed miRNAs between 23SSI and 23DSI and their different functions indicated that more genes or metabolic pathways in paired mature females were inhibited than those in unpaired ones. The results suggested that after pairing, specific miRNAs regulated gene expression to lead to female sexual maturation.Parasites & Vectors 04/2014; 7(1):177. · 3.25 Impact Factor
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ABSTRACT: Schistosomes, a class of parasitic trematode worms, cause schistosomiasis. Accumulating evidence suggests that microRNAs (miRNAs)-small, non-coding RNAs that are known to play critical regulatory roles in many organisms-may be involved in schistosome development and sexual maturation, as well as the pathogenesis of schistosomiasis. Schistosoma miRNAs, such as Bantam and miR-10, may be involved in the pathological processes of schistosomiasis, and recent studies suggest that schistosome-specific miRNAs (e.g., Bantam, miR-3479-3p) in the bloodstream of a final host could be used as biomarkers for schistosomiasis diagnosis. Furthermore, aberrant miRNAs, such as miR-223 and miR-454, can be produced by a host in response to schistosome infection, and these miRNAs may contribute to the pathogenesis of schistosomiasis-associated liver injury. Here, we summarize recent progress evaluating the relationship between schistosome miRNAs and schistosomiasis and discuss how these miRNAs can mediate the pathogenesis of schistosomiasis and be used as biomarkers for schistosomiasis diagnosis.Frontiers in Cellular and Infection Microbiology 11/2014; 4:165. · 2.62 Impact Factor
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ABSTRACT: Schistosomiasis, caused by dioecious flatworms in the genus Schistosoma, is torturing people from many developing countries nowadays and frequently leads to severe morbidity and mortality of the patients. Praziquantel based chemotherapy and morbidity control for this disease adopted currently necessitate viable and efficient diagnostic technologies. Fortunately, those "-omics" researches, which rely on high-throughput experimental technologies to produce massive amounts of informative data, have substantially contributed to the exploitation and innovation of diagnostic tools of schistosomiasis. In its first section, this review provides a concise conclusion on the progresses pertaining to schistosomal "-omics" researches to date, followed by a comprehensive section on the diagnostic methods of schistosomiasis, especially those innovative ones based on the detection of antibodies, antigens, nucleic acids, and metabolites with a focus on those achievements inspired by "-omics" researches. Finally, suggestions about the design of future diagnostic tools of schistosomiasis are proposed, in order to better harness those data produced by "-omics" studies.Frontiers in Microbiology 06/2014; 5:313. · 3.94 Impact Factor