Differential microRNA expression profiles and predicted miRNA–mRNA regulatory networks in human macrophage-like cells infected with Leishmania infantum

Résumé fourni par la source

MicroRNAs (miRNAs) regulate gene expression and play a crucial role in numerous diseases, including infections. Leishmaniasis is a neglected infectious disease occurring in different forms (i.e., cutaneous, mucocutaneous, and visceral) caused by a protozoan belonging to the Leishmania genus. The parasite infects mainly the macrophages, establishing a niche permissive for its proliferation. Leishmania parasites are known to modulate host gene expression, including miRNAs; however, the specific role of these miRNAs in driving host transcriptomic changes remains to be fully characterized. The aim of this work was to study miRNA expression profile in human macrophage-like cells infected by L. infantum, the causative agent of visceral and cutaneous leishmaniasis in the Mediterranean region. Moreover, we attempted to identify putative miRNA-mRNA interactions based on the mRNA expression changes previously described. To this end, small RNA-seq was performed in U937 cells infected with L. infantum after 24 h and 48 h, and differentially expressed miRNA were identified and validated through qPCR. For identifying miRNA-mRNA interactions, the upregulated and downregulated miRNAs at 24 h (n = 24, 10) and 48 h (n = 25, 12) post-infection were analyzed against downregulated and upregulated mRNA, respectively, through the mirDIP (microRNA Data Integration Portal) database. A large fraction of dysregulated protein-coding transcripts was predicted to be affected by dysregulated miRNAs identified in the same samples. We focused in particular on protein-coding genes involved in previously identified dysregulated pathways characterizing L. infantum infection (i.e., cholesterol and lipid metabolism, VEGF-VEGFR2 and NF2EL2-related pathways) and transcription factors (TFs). Notably, the fraction of protein coding transcripts predicted to be targeted by dysregulated miRNAs was particularly high in TFs, indicating that changes in a small set of miRNAs may have great impact on macrophage expression profile and phenotype.

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