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Published on: January 17, 2014
miR-4687-5p Affects Intracellular Survival of Mycobacterium tuberculosis through Its Regulation of NRAMP1 Expression
Chaoqun Meng1,2,3, Guangxin Chen1,2, Yue Liu1,2
1The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province, Institute of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan 030006, China.
Abstract:
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 Mycobacterium tuberculosis (Mtb)-infected A549 cells. Concomitantly, we detected a reduced level of NRAMP1 expression, suggesting that NRAMP1 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 Mtb loads post-infection, indicating that miR-4687-5p promotes the intracellular survival of Mtb 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 Mtb. The results presented in our study suggest that miR-4687-5p may be indicative of the susceptibility of Mtb infection to humans and could act as a potential therapeutic target for tuberculosis treatment.
Insights
MicroRNAs (miRNAs) regulate gene expression. This study identifies miR-4687-5p as a key factor in tuberculosis (TB) pathogenesis, promoting Mycobacterium tuberculosis survival by downregulating NRAMP1, suggesting it as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Immunology
- Microbiology
Background:
- Tuberculosis (TB) remains a major global health threat.
- MicroRNAs (miRNAs) are crucial regulators of gene expression.
- Altered miRNA expression is observed during Mycobacterium tuberculosis (Mtb) infection.
Purpose of the Study:
- To investigate the role of specific miRNAs in TB pathogenesis.
- To identify regulatory interactions between miRNAs and host genes involved in Mtb infection.
- To explore potential therapeutic targets for TB treatment.
Main Methods:
- Luciferase assays to confirm miRNA-target binding.
- Quantification of miRNA and NRAMP1 expression in Mtb-infected cells.
- Infection experiments with miRNA transfection to assess Mtb loads, apoptosis, and cell proliferation.
Main Results:
- miR-4687-5p directly targets the 3'-untranslated region of NRAMP1.
- miR-4687-5p expression increases, while NRAMP1 expression decreases in Mtb-infected cells.
- Transfection of miR-4687-5p enhances intracellular Mtb survival, increases apoptosis, and reduces cell proliferation.
Conclusions:
- miR-4687-5p promotes Mtb intracellular survival by downregulating NRAMP1.
- miR-4687-5p may serve as a biomarker for Mtb infection susceptibility.
- miR-4687-5p represents a potential therapeutic target for tuberculosis.
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