hsa-let-7b-5p facilitates Mycobacterium tuberculosis survival in THP-1 human macrophages by Fas down regulation

Abstract

Tuberculosis continues to be one of the deadliest infectious disease worldwide. MicroRNAs (miRNAs) are small non-coding entities that play critical role as post-transcriptional regulators and are transcriptionally deregulated upon mycobacterial infection. In this study, we found significant upregulation of hsa-let-7b-5p in Mycobacterium tuberculosis (MTB) infected THP-1 human macrophages. Concomitantly, we detected the reduced level of Fas protein, one of the targets of hsa-let-7b-5p, in MTB infected THP-1 macrophages. Using luciferase assay a direct interaction between hsa-let-7b-5p and the Fas 3'-untranslated region (UTR) was established. Inhibition of hsa-let-7b-5p augmented the apoptosis of THP-1 cells enabling enhanced clearance of MTB. Our findings suggest that hsa-let-7b-5p helps intracellular survival of MTB in THP-1 cells by down-regulating Fas protein level. This highlights hsa-let-7b-5p as a potential therapeutic target for tuberculosis treatment.