Human microRNAs in host-parasite interaction: a review

Abstract

MicroRNAs (miRNAs) are a group of small noncoding RNA molecules with significant capacity to regulate the gene expression at the post-transcriptional level in a sequence-specific manner either through translation repression or mRNA degradation triggering a fine-tuning biological impact. They have been implicated in several processes, including cell growth and development, signal transduction, cell proliferation and differentiation, metabolism, apoptosis, inflammation, and immune response modulation. However, over the last few years, extensive studies have shown the relevance of miRNAs in human pathophysiology. Common human parasitic diseases, such as Malaria, Leishmaniasis, Amoebiasis, Chagas disease, Schistosomiasis, Toxoplasmosis, Cryptosporidiosis, Clonorchiasis, and Echinococcosis are the leading cause of death worldwide. Thus, identifying and characterizing parasite-specific miRNAs and their host targets, as well as host-related miRNAs, are important for a deeper understanding of the pathophysiology of parasite-specific diseases at the molecular level. In this review, we have demonstrated the impact of human microRNAs during host-parasite interaction as well as their potential to be used for diagnosis and prognosis purposes.

Keywords: Biomarker; Human parasitic diseases; Pathophysiology; Prognosis; microRNAs.

Fig. 1

The canonical pathway of miRNA biogenesis. a In the nucleus, the miRNA gene is transcribed by RNA polymerase II and then fold into a long pri-miRNA with a hairpin structure. The long pri-miRNA is then cleaved by the microprocessor complex made up of Drosha and DGCR8 (Pasha) proteins, generating a precursor miRNA (pre-miRNA). b Exportin-5 binds to the pre-miRNA and facilitates its export to the cytoplasm. In the cytoplasm, the type III RNase Dicer complex with the double-stranded RNA binding protein TRBP and PACT cleaves the precursor’s hairpin and the resulting duplex is isolated by a helicase enzyme. Finally, the functional strand is loaded together with the Argonaute (AGO) protein into the RNA-induced silencing complex (RISC) to target mRNAs by sequence complementary binding and mediates gene suppression through mechanisms of either translational repression or mRNA degradation

Fig. 2

A graphical illustration of human microRNAs and their targets profile during host−parasite interaction of the most important insect vector transmitted parasitic diseases discussed in this review: (a) Malaria (b) Leishmaniasis, and (c) Chagas disease