Multifunctional Roles of MicroRNAs in Schistosomiasis

Abstract

Schistosomiasis is a parasitic disease that is caused by helminths of the genus Schistosoma. The dioecious schistosomes mate and lay eggs after undergoing a complex life cycle. Schistosome eggs are mostly responsible for the transmission of schistosomiasis and chronic fibrotic disease induced by egg antigens is the main cause of the high mortality rate. Currently, chemotherapy with praziquantel (PZQ) is the only effective treatment against schistosomiasis, although the potential of drug resistance remains a concern. Hence, there is an urgent demand for new and effective strategies to combat schistosomiasis, which is the second most prevalent parasitic disease after malaria. MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal regulatory roles in many organisms, including the development and sexual maturation of schistosomes. Thus, miRNAs are potential targets for treatment of schistosomiasis. Moreover, miRNAs can serve as multifunctional “nano-tools” for cross-species delivery in order to regulate host-parasite interactions. In this review, the multifunctional roles of miRNAs in the growth and development of schistosomes are discussed. The various regulatory functions of host-derived and worm-derived miRNAs on the progression of schistosomiasis are also thoroughly addressed, especially the promotional and inhibitory effects on schistosome-induced liver fibrosis. Additionally, the potential of miRNAs as biomarkers for the diagnosis and treatment of schistosomiasis is considered.

Single-sex schistosomiasis: a mini review

“…MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate the expression of target genes at the posttranscriptional level by binding to the 3'-and 5'-untranslated regions and coding sequences in order to repress translation or initiate degradation (67). Schistosome-derived miRNAs have been implicated in schistosome development and host-parasite interactions in schistosomiasis (68)(69)(70). The miRNA expression profiles of SF and MF S. japonicum have been reported (71,72).…”

“…Several unresolved challenges and problems remain due to insufficient knowledge of single-sex schistosomes, including (i) the application of traditional egg-based parasitological tests for detection of single-sex infections; (ii) detection of antigens or nucleic acids as diagnostic criteria, as positive results might be due to past schistosome exposure or cross-reactions, rather than a single-sex schistosome infection ( 89 , 90 ), and the reliance on morphological observations after dissection, which can create logistical difficulties; (iii) greater resistance of long-lived single-sex schistosomes to PZQ than paired worms ( 26 ); and (iv) the application of Omics studies to identify potential diagnostic and therapeutic targets. Extracellular vesicles (EVs) released from schistosome eggs and worms at different developmental stages were identified and considered to be important vectors in the regulation of host-parasite interactions ( 70 ). Studies have reported that the cargo of schistosome-derived EVs include sja-miR-1 ( 91 ), sma-miR-10 ( 92 ), sja-miR-71a ( 69 ), sja-miR-125b ( 93 ), sja-miR-2162 ( 94 ), sja-bantam ( 93 ) and novel sja-miRNA-33 ( 95 ), which mediate cross-species host-parasite interactions.…”

microRNAs: Critical Players during Helminth Infections

“…Schistosoma -derived miRNAs can be detected in the serum/plasma of the host [ 109 , 110 , 111 ]. Particularly, sma-miR-277, sma-miR-3479-3p, and sma-bantam have been detected in the serum of S. mansoni -infected mice and patients [ 109 ].…”

“…Others, such as sja-miR-2c-5p, sja-miR-277, and sja-miR-3479, significantly correlate with fecal egg counts and hepatic egg burden [ 110 , 112 ]. Therefore, it has been proposed that these parasite-derived circulating miRNAs could serve as tissue or serum biomarkers for detecting human S. japonicum infection, even in low-intensity infections [ 109 , 110 , 111 ].…”