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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

Y Chen, C Wu, M Lin, C Hsiao, C P Lee
European Respiratory Journal 2022 60: 598; DOI: 10.1183/13993003.congress-2022.598
Y Chen
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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C Wu
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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M Lin
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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C Hsiao
2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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C P Lee
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Abstract

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.

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  • Immunology
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Footnotes

Cite 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).

  • Copyright ©the authors 2022
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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
Y Chen, C Wu, M Lin, C Hsiao, C P Lee
European Respiratory Journal Sep 2022, 60 (suppl 66) 598; DOI: 10.1183/13993003.congress-2022.598

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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
Y Chen, C Wu, M Lin, C Hsiao, C P Lee
European Respiratory Journal Sep 2022, 60 (suppl 66) 598; DOI: 10.1183/13993003.congress-2022.598
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  • Active tuberculosis and malignance: a 5 year retrospective study
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Show more 10.02 - Tuberculosis and non-tuberculous mycobacterial diseases

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