In silico identification of human microRNAs pointing centrin genes in Leishmania donovani: Considering the RNAi-mediated gene control

Abstract

Leishmaniasis, a parasitic disease caused by different species of the protozoa parasite Leishmania, is a neglected tropical human disease that is endemic in about a hundred countries worldwide. According to the World Health Organization (WHO), the annual incidence of cutaneous leishmaniasis (CL) is estimated to be 0.7–1.2 million cases globally, whereas the annual incidence of visceral leishmaniasis is estimated to be 0.2–0.4 million cases. In many eukaryotic organisms, including human beings and protozoan parasites, centrin genes encode proteins that play essential roles within the centrosome or basal body. Human microRNAs (miRNAs) have been linked to several infectious and non-infectious diseases associated with pathogen–host interactions, and they play the emphatic roles as gene expression regulators. In this study, we used the MirTarget bioinformatics tool, which is a machine learning-based approach implemented in miRDB, to predict the target of human miRNAs in Leishmania donovani centrin genes. For cross-validation, we utilized additional prediction algorithms, namely, RNA22 and RNAhybrid, targeting all five centrin isotypes. The centrin-3 (LDBPK_342160) and putative centrin-5 (NC_018236.1) genes in L. donovani were targeted by eight and twelve human miRNAs, respectively, among 2,635 known miRNAs (miRBase). hsa-miR-5193 consistently targeted both genes. Using TargetScan, TarBase, miRecords, and miRTarBase, we identified miRNA targets and off-targets in human homologs of centrin, inflammation, and immune-responsive genes. Significant targets were screened based on GO terminologies and KEGG pathway-enrichment analysis (Log10 p-value >0.0001). In silico tools that predict the biological roles of human miRNAs as primary gene regulators in pathogen–host interactions help unravel the regulatory patterns of these miRNAs, particularly in the early stages of inflammatory responses. It is also noted that these miRNAs played an important role in the late phase of adaptive immune response, inclusively their impacts on the immune system’s response to L. donovani.