Overexpression of microRNA-340-5p Ameliorates Inflammatory Response and Intracellular Survival of Mycobacterium Tuberculosis in Alveolar Type II Cells

Infect Drug Resist. 2021 Apr 21:14:1573-1584. doi: 10.2147/IDR.S291867. eCollection 2021.

Abstract

Background: The importance of microRNAs (miRs) has been documented in infections. This study estimated the role of miR-340-5p in Mycobacterium tuberculosis (Mtb)-infected alveolar type II cells.

Methods: The microarray of GEO database was analyzed to find the differentially expressed miRs caused by Mtb infection, and miR-340-5p was selected as the research object. The effects of Mtb infection on A549 cells were studied by MTT, CFU, EdU, flow cytometry and ELISA assays. miR-340-5p expression was altered in Mtb-infected A549 cells. The downstream target of miR-340-5p was found by bioinformatics analysis and verified by the rescue experiment. The pathways regulated by miR-340-5p and its target gene were further studied.

Results: Mtb infection suppressed the activity of A549 cells and promoted the release of inflammatory factors. Mtb infection inhibited miR-340-5p expression. Overexpression of miR-340-5p enhanced the resistance of A549 cells to Mtb infection. Moreover, miR-340-5p targeted TMED7. Overexpression of TMED7 reversed the protective effect of miR-340-5p on Mtb-infected A549 cells. miR-340-5p inhibited the activation of NF-κB by targeting TMED7.

Conclusion: miR-340-5p inhibits the activation of NF-κB by targeting TMED7, thus alleviating the injury of A549 cells caused by Mtb infection. This study may offer a novel approach to Mtb infection.

Keywords: Mycobacterium tuberculosis; NF-κB; TMED7; alveolar type II cells; microRNA-340-5p.

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