TY - DATA T1 - MicroRNA expression profiling of Leishmania donovani-infected host cells uncovers the regulatory role of MIR30A-3p in host autophagy PY - 2016/08/19 AU - Alok Kumar Singh AU - Rajeev Kumar Pandey AU - Chandrima Shaha AU - Rentala Madhubala UR - https://tandf.figshare.com/articles/dataset/MicroRNA_expression_profiling_of_i_Leishmania_donovani_i_-infected_host_cells_uncovers_the_regulatory_role_of_i_MIR30A-3p_i_in_host_autophagy/3502025 DO - 10.6084/m9.figshare.3502025.v2 L4 - https://ndownloader.figshare.com/files/5534057 L4 - https://ndownloader.figshare.com/files/5534060 KW - autophagy KW - BECN1 KW - gene expression KW - human monocyte-derived macrophages KW - Leishmania donovani KW - microRNAs KW - MIR30A-3p KW - THP-1 cells N2 - Leishmania 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, 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). 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 reveals for the first time a novel role of MIR30A-3p in regulating autophagy-mediated L. donovani elimination by targeting BECN1. The present study has significant impact for the treatment of visceral leishmaniasis. ER -