Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages. Issue 18 (16th September 2016)

• Record Type: Journal Article
• Authors: Zhang, Guoliang; Liu, Xi; Wang, Wenfei; Cai, Yi; Li, Shaoyuan; Chen, Qi; Liao, Mingfeng; Zhang, Mingxia; Zeng, Gucheng; Zhou, Boping; Feng, Carl G.; Chen, Xinchun
• Is Part Of: Cell cycle. Volume 15:Issue 18(2016)
• Page Start: 2527
• Page End: 2538
• Publication Date: 2016-09-16
• Subjects: apoptosis -- JNK2 -- macrophages -- mycobacterial -- miR-20a-5p; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2016.1215386
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Induction of cell apoptosis is one of the major host defense mechanisms through which macrophages control Mycobacterium tuberculosis (Mtb) infection. However, the mechanisms underlying macrophage apoptosis triggered by Mtb infection are still largely unknown. In this study, a microarray profiling survey revealed 14 miRNAs were down-regulated in CD14+ monocytes from active pulmonary tuberculosis patients, and only the reduction of miR-20a-5p could be reversed after successful anti-tuberculosis treatment. Validation of miR-20a-5p expression was confirmed using real time qPCR. Moreover, miR-20a-5p expression also decreased in differentiated THP-1 macrophages after mycobacterial infection in vitro. Functional assays through forced or inhibited expression of miR-20a-5p in THP-1 macrophages demonstrated that miR-20a-5p functioned as a negative regulator of mycobacterial-triggered apoptosis. Importantly, inhibition of miR-20a-5p expression resulted in more efficient mycobacterial clearance from infected THP-1 macrophages while miR-20a-5p overexpression promoted mycobacterial survival. Mechanistically, miR-20a-5p was demonstrated to regulate Bim expression in a JNK2-dependent manner, unlike Bcl2, and luciferase assay showed JNK2 was a novel direct target of miR-20a-5p. Together, our findings indicate that downregulation of miR-20a-5p triggers macrophage apoptosis as a novel mechanism for host defense against mycobacterial infection.