PT  - JOURNAL ARTICLE
AU  - Chen, Y
AU  - Wu, C
AU  - Lin, M
AU  - Hsiao, C
AU  - Lee, C P
TI  - Next generation sequencing reveals miR-431-3p and miR-1303 as immune-regulatory microRNA for active pulmonary tuberculosis through targeting MDR1/MMP16/RIPOR2 and ATG5 signaling
AID  - 10.1183/13993003.congress-2022.598
DP  - 2022 Sep 04
TA  - European Respiratory Journal
PG  - 598
VI  - 60
IP  - suppl 66
4099  - http://erj.ersjournals.com/content/60/suppl_66/598.short
4100  - http://erj.ersjournals.com/content/60/suppl_66/598.full
SO  - Eur Respir J2022 Sep 04; 60
AB  - Background: Host-directed therapy, such as RNA therapeutics, in combination with current standard antimicrobial treatments would improve disease outcome through bypassing the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (M.tb).Methods: We sought to screen for microRNA with immune-regulatory functions against M.tb by using next generation sequencing.Results: Twenty three differentially expressed microRNAs were identified between 12 active pulmonary TB patients and 4 healthy subjects, and 35 microRNAs before and after 6-month anti-TB therapy. Enriched predicted target pathways based on biological process included cell apoptosis, pyruvate metabolic, macroautophagy. We verified miR-431-3p down-regulation and miR-1303 up-regulation accompanied with corresponding changes in their target genes in an independent validation cohort of 46 active TB patients, 30 latent TB infection subjects, and 24 non-infected healthy subjects. In vitro experiments of transfections with miR-431-3p mimic and miR-1303 Si RNA in THP-1 cells under ESAT-6 stimuli showed that miR-431-3p and miR-1303 were capable to augment and suppress apoptosis/phagocytosis of macrophage via up regulating MDR1/MMP16/RIPOR2 and down regulating ATG5, respectively.Conclusions: This provides a proof of concept for microRNA-based therapy for active TB disease. FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 598.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).