MicroRNA expression profiling of <i>Leishmania donovani</i>-infected host cells uncovers the regulatory role of MIR30A-3p in host autophagy SinghAlok Kumar Kumar PandeyRajeev ShahaChandrima MadhubalaRentala 2016 <p><i>Leishmania</i> is an obligate intracellular parasite that replicates inside phagolysosomes or parasitophorous vacuoles (PV) of the monocyte/macrophage lineage. 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, <i>MIR30A-3p</i> in modulation of host cell macroautophagy/autophagy after infection with <i>L. donovani</i>. Our in vitro studies showed that <i>MIR30A-3p</i> expression was significantly enhanced after <i>L. donovani</i> infection in a time-dependent manner. Transient transfection with a <i>MIR30A-3p</i> inhibitor followed by <i>L. donovani</i> infection promoted the autophagic response and decreased the intracellular parasite burden in both THP-1 cells and human monocyte-derived macrophages (HsMDM). 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 <i>L. donovani</i> infection. Pretreatment of <i>L. donovani</i>-infected macrophages with the <i>MIR30A-3p</i> mimic decreased and with antagomir increased the expression of BECN1 protein. We demonstrate that <i>BECN1</i> is a potential target of <i>MIR30A-3p</i> and this miRNA negatively regulates <i>BECN1</i> expression. Our present study reveals for the first time a novel role of <i>MIR30A-3p</i> in regulating autophagy-mediated <i>L. donovani</i> elimination by targeting <i>BECN1</i>. The present study has significant impact for the treatment of visceral leishmaniasis.</p>