Elucidating miR-146a-3p as a key player in autophagy and lipid metabolism in Leishmania major infection

Autophagy is a key step involved in many unicellular eukaryotic diseases, including leishmaniasis, for cellular remodelling and differentiation during parasite's lifecycle. Lipids play a significant role in the infection process that begins with Leishmania major invading host cells. MicroRNAs (...

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Bibliographic Details
Published in:Experimental parasitology 2024-05, Vol.260, p.108745-108745, Article 108745
Main Authors: Ingale, Prajakta, Singh, Shailza
Format: Article
Language:English
Subjects:
ATG7
Autophagy
HPGD
Leishmania major
Lipid droplets
microRNAs
THP-1 cells
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Summary:Autophagy is a key step involved in many unicellular eukaryotic diseases, including leishmaniasis, for cellular remodelling and differentiation during parasite's lifecycle. Lipids play a significant role in the infection process that begins with Leishmania major invading host cells. MicroRNAs (miRNAs), a family of small, 22–24 nucleotide noncoding regulatory RNAs, target mRNAs to modify gene expression and, subsequently, proteome output may have a regulatory role in altering the host cell processes. We observed miR-146a-3p expression increases in a time-dependent manner post Leishmania major infection. Transfecting miR-146a-3p mimic increases the expression of ATG7, an autophagy gene that encodes an E1-like enzyme in two ubiquitin-like conjugation systems required for autophagosome progression. HPGD (15-hydroxyprostaglandin dehydrogenase) operates as an enzyme, converting prostaglandin to its non-active form. Microarray data and western studies reveal that miR-146a-3p targets and inhibits HPGD, thereby increasing prostaglandin activity in lipid droplets. Herein, our research focuses on miR-146a-3p, which boosts ATG7 expression while reducing HPGD post Leishmania major infections helping us comprehend the intricate network of microRNA, autophagy, and lipid metabolism in leishmaniasis. [Display omitted] •Autophagy and Lipid metabolism plays critical role in establishing Leishmania major infection.•miR-146a-3p targets ATG7 to upregulate it post Leishmania major infection.•miR-146a-3p targets HPGD to downregulate it after Leishmania major infection. HPGD is an important enzyme for PGE2 breakdown.
ISSN:0014-4894
1090-2449
DOI:10.1016/j.exppara.2024.108745