LncRNA MEG3 control Mycobacterium Tuberculosis infection via controlled MiR-145-5p expression and modulation of macrophages proliferation

Abstract

Background: Mycobacterium tuberculosis (Mtb) is an intractable pathogen for humans to overcome. While as an important part of innate immunity, macrophages play an important role in resisting foreign pathogenic microorganisms, and it has been proved that there is a close relationship between macrophages and Mtb. In recent years, with the in-depth study of LncRNA, there have been crucial breakthroughs in the diagnosis and treatment of a number of diseases, and understanding the impact of LncRNA on Mtb may also be conducive to providing new therapeutic targets for tuberculosis prevention and treatment in the future. Therefore, this study explore the role of MEG3 in the proliferation and apoptosis of Mtb-infected macrophages.

Methods: Between September 2017 and September 2019, 84 consecutive pulmonary Mtd patients admitted to our hospital were selected as the observation group (OG), and concurrently, 88 healthy controls were selected as the control group (CG). MEG3 and miR-145-5p in peripheral blood of the two groups were detected, and their diagnostic value in pulmonary tuberculosis (PTB) was analyzed by receiver operating characteristic (ROC) curves. In addition, Bacillus Calmette-Guérin (BCG) and mouse Raw264.7 macrophage strains were purchased to establish the Mtb-infected macrophage model. Colony forming unit (CFU) and flow cytometry were employed to determine the effects of MEG3 and miR-145-5p on macrophages, and the correlation between the two was performed by dual-luciferase reporter (DLR) assay.

Results: MEG3 was highly expressed in PTB, while miR-145-5p was lowly expressed (P < 0.050). ROC analysis demonstrated that both MEG3 and miR-145-5p enjoyed favorable predictive value for the occurrence of PTB (P < 0.001). In the Mtb-infected macrophage model, MEG3 decreased (P < 0.050) while miR-145-5p increased with the time of infection (P < 0.050). Inhibited MEG3 and overexpressed miR-145-5p resulted in increased CFU and decreased apoptosis ability of macrophages (P < 0.050). The DLR assay identified a targeting relationship between miR-145-5p and MEG3 (P < 0.050). The increase of MEG3 could inhibit the expression of in miR-145-5p (P < 0.050).

Conclusion: MEG3 affects the biological activity of Mtb-infected macrophages by targeting miR-145-5p, which may be the key to the diagnosis and treatment of PTB and even all kinds of tuberculosis in the future.

Keywords: Apoptosis; MEG3; Macrophages; Mtb; Proliferation; miR-145-5p.