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• W2037432461 endingPage "e1003697" @default.
• W2037432461 startingPage "e1003697" @default.
• W2037432461 abstract "Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that infects one-third of the global population. It can live within macrophages owning to its ability to arrest phagolysosome biogenesis. Autophagy has recently been identified as an effective way to control the intracellular mycobacteria by enhancing phagosome maturation. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-mycobacterial response. Both in vivo and in vitro studies showed that miR-155 expression was significantly enhanced after mycobacterial infection. Forced expression of miR-155 accelerated the autophagic response in macrophages, thus promoting the maturation of mycobacterial phagosomes and decreasing the survival rate of intracellular mycobacteria, while transfection with miR-155 inhibitor increased mycobacterial survival. However, macrophage-mediated mycobacterial phagocytosis was not affected after miR-155 overexpression or inhibition. Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7) reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3′-untranslated region of Ras homologue enriched in brain (Rheb), a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. Our results reveal a novel role of miR-155 in regulating autophagy-mediated mycobacterial elimination by targeting Rheb, and provide potential targets for clinical treatment." @default.
• W2037432461 created "2016-06-24" @default.
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• W2037432461 date "2013-10-10" @default.
• W2037432461 modified "2023-10-11" @default.
• W2037432461 title "MicroRNA-155 Promotes Autophagy to Eliminate Intracellular Mycobacteria by Targeting Rheb" @default.
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• W2037432461 doi "https://doi.org/10.1371/journal.ppat.1003697" @default.
• W2037432461 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3795043" @default.
• W2037432461 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24130493" @default.
• W2037432461 hasPublicationYear "2013" @default.
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