摘要：

Cholesterol reduction by intracellular protozoan parasiteLeishmania donovani,causative agent of leishmaniasis, impairs antigen presentation, pro-inflammatory cytokine secretion and host-protective membrane-receptor signaling in macrophages. Here, we studied the miRNA mediated regulation of cholesterol biosynthetic genes to understand the possible mechanism ofLeishmania donovani-inducedcholesterol reduction and therapeutic importance of miRNAs in leishmaniasis. System-scale genome-wide microtranscriptome screening was performed to identify the miRNAs involved in the regulation of expression of key cholesterol biosynthesis regulatory genes through miRanda3.0. 11 miRNAs out of 2823, showing complementarity with cholesterol biosynthetic genes werefinallyselected for expression analysis. These selected miRNAs were differentially regulated in THP-1 derived macrophages and in primary human macrophages byL. donovani. Correlation of expression and target validation through luciferase assay suggested two key miRNAs, hsa-miR-1303 and hsa-miR-874-3pregulating the key geneshmgcrandhmgcs1respectively. Inhibition of hsa-mir-1303 and hsa-miR-874-3p augmented the expression of targets and reduced the parasitemia in macrophages.This study will also provide the platform for the development of miRNA-based therapy against leishmaniasis.

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