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Data · dataset · 2016

MicroRNA expression profiling of Leishmania donovani -infected host cells uncovers the regulatory role of MIR30A-3p in host autophagy

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Leishmania is an obligate intracellular parasite that replicates inside phagolysosomes or parasitophorous vacuole (PV) of the monocyte/macrophage lineage.

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It reprograms macrophages and produces a metabolic state conducive to successful infection and multiplication. MicroRNAs (miRNAs), a class of small 22 to 24 nucleotide noncoding regulatory RNAs alter the gene expression and consequently proteome output by targeting mRNAs, may play a regulatory role in modulating host cell functions.

In the present study, we demonstrate the novel regulatory role of host microRNA, MIR30A-3p in modulation of host cell macroautophagy/autophagy after infection with L. donovani . Our in vitro studies showed that MIR30A-3p expression was significantly enhanced after L. donovani infection in a time-dependent manner. Transient transfection with a MIR30A-3p inhibitor followed by L. donovani infection promoted the autophagic response and decreased the intracellular parasite burden in both THP-1 cells and human monocyte-derived macrophages (HsMDM).

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BECN1/Beclin 1, the mammalian ortholog of yeast Vps30/Atg6, is a key autophagy-promoting protein that plays a key role in the regulation of cell death and survival. We report BECN1 dependent modulation of host cell autophagy in response to L. donovani infection. Pretreatment of L. donovani -infected macrophages with the MIR30A-3p mimic decreased and with antagomir increased the expression of BECN1 protein.

We demonstrate that BECN1 is a potential target of MIR30A-3p and this miRNA negatively regulates BECN1 expression. Our present study for the first time reveals a novel role of MIR30A-3p in regulating autophagy-mediated L. donovani elimination by targeting BECN1 . The present study has significant impact in the treatment of visceral leishmaniasis.

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DataCite10.6084/m9.figshare.3502025.v111 d agoJSON v1
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