miR-4687-5p Affects Intracellular Survival of <i>Mycobacterium tuberculosis</i> through Its Regulation of NRAMP1 Expression in A549 Cells

Tuberculosis (TB), as one of the leading causes of death, poses a serious predicament to the world. MicroRNAs (miRNAs) play a role in the post-transcriptional regulation of gene expression. It has been reported that the expression of miRNAs changes upon mycobacterial infection; the screening and ide...

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Main Authors: Chaoqun Meng, Guangxin Chen, Yue Liu, Da Wen, Jia Cui, Li Dong, Zhiqiang Yang, Hangting Meng, Yuanting Gao, Jiao Feng, Xiaogang Cui, Changxin Wu
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/12/1/227
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Summary:Tuberculosis (TB), as one of the leading causes of death, poses a serious predicament to the world. MicroRNAs (miRNAs) play a role in the post-transcriptional regulation of gene expression. It has been reported that the expression of miRNAs changes upon mycobacterial infection; the screening and identification of miRNAs regulating the expression of genes could benefit our understanding of TB pathogenesis and generate effective strategies for its control and prevention. In this study, luciferase assays showed that miR-4687-5p is bound to the 3′-untranslated region of natural resistance-associated macrophage protein 1 (NRAMP1). Additionally, we found a significant increase in miR-4687-5p expression in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>)-infected A549 cells. Concomitantly, we detected a reduced level of NRAMP1 expression, suggesting that <i>NRAMP1</i> is one of the targets of miR-4687-5p. Infection experiments evidenced that the transfection of miR-4687-5p induced a decrease in NRAMP1 expression and increased intracellular <i>Mtb</i> loads post-infection, indicating that miR-4687-5p promotes the intracellular survival of <i>Mtb</i> through its downregulation of the NRAMP1 protein level. We also found that the transfection of miR-4687-5p induced increased apoptosis and decreased cell proliferation post-infection with <i>Mtb</i>. The results presented in our study suggest that miR-4687-5p may be indicative of the susceptibility of <i>Mtb</i> infection to humans and could act as a potential therapeutic target for tuberculosis treatment.
ISSN:2076-2607