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: SUMMARY Circulating microRNAs (miRNAs) have received considerable attention as a novel class of biomarkers for the diagnosis of cancer and as signalling molecules in mediating intercellular communication. Schistosomes, the causative agents of schistosomiasis, live in the blood vessels of a mammalian host in the adult stage. In the present study, we characterized schistosome-specific small RNA populations in the plasma of rabbits infected with Schistosoma japonicum (S. japonicum) using a deep sequencing method and then identified five schistosome-specific miRNAs, including four known miRNAs (Bantam, miR-3479, miR-10 and miR-3096), and one novel miRNA (miR-0001, miRBase ID: sja-miR-8185). Four of the five schistosome-specific miRNAs were also detected by real-time RT-PCR in the plasma of S. japonicum-infected mice. In addition, our study indicated that schistosome Argonaute 2/3 may be an excretory-secretory (ES) protein. In summary, our findings are expected to provide useful information for further development of novel biomarkers for the diagnosis of schistosomiasis and also for deeper understanding of the mechanism of host-parasite interaction.Parasitology 08/2013; · 2.36 Impact Factor
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ABSTRACT: Abstract Infectious agents have been associated with cancer due to activation of pro-carcinogenic inflammatory processes within their host. Several reports, however, indicate that specific pathogens may be able to elicit anti-tumor immune responses that can lead to protection from tumorigenesis or cancer regression. Amongst these "beneficial" pathogens are some helminthic parasites that have already been connected with prevention of autoimmune diseases and allergies, immune conditions increasingly associated with cancer. Even though helminths have co-existed with humans and their ancestors for millions of years, investigations of their impact on human (patho)physiology are relatively new and the functions of components that can explain the helminth bi-directional influence on carcinogenesis are not well understood. This review aims to discuss evidence for the helminth-induced immune, genetic, epigenetic, proteomic, hormonal and metabolic changes that may ultimately mediate the potential pro- or anti-carcinogenic role of helminths. This overview may serve future investigations in clarifying the tumorigenic role of the most common helminthic parasites. It may also inspire the development of anti-cancer regimens and vaccines, in parallel to ongoing efforts of using helminth-based components for the prevention and/or treatment of autoimmune diseases and allergies.Critical Reviews in Clinical Laboratory Sciences 03/2014; · 3.78 Impact Factor