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

hsa-let-7b-5p 通过 Fas 下调促进结核分枝杆菌在 THP-1 人巨噬细胞中存活

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作者:Ashutosh Tripathi, Vishal Srivastava, Bhupendra N Singh

Abstract

Tuberculosis continues to be one of the deadliest infectious diseases 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 (3΄-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 downregulating Fas protein level. This highlights hsa-let-7b-5p as a potential therapeutic target for tuberculosis treatment.

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