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Next generation sequencing reveals miR-431-3p/miR-1303 as immune-regulating microRNAs for active tuberculosis.
Chen, Yung-Che; Hsiao, Chang-Chun; Wu, Chao-Chien; Chao, Tung-Ying; Leung, Sum-Yee; Chang, Yu-Ping; Tseng, Chia-Cheng; Lee, Chiu-Ping; Hsu, Po-Yuan; Wang, Ting-Ya; Wang, Po-Wen; Chen, Ting-Wen; Lin, Meng-Chih.
Afiliación
  • Chen YC; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address: chestr@cgmh.org.tw.
  • Hsiao CC; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; Graduate Institute of Clinical Medical Sciences, Taiwan.
  • Wu CC; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
  • Chao TY; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
  • Leung SY; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
  • Chang YP; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
  • Tseng CC; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
  • Lee CP; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
  • Hsu PY; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
  • Wang TY; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
  • Wang PW; Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan.
  • Chen TW; Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan. Electronic address: dodochen@nctu.edu.tw.
  • Lin MC; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan. Electronic address: mengchih@cgmh.org.tw.
J Infect ; 85(5): 519-533, 2022 11.
Article en En | MEDLINE | ID: mdl-36057384
OBJECTIVES: RNA therapeutics is an emerging field that widens the range of treatable targets and would improve disease outcome through bypassing the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (M.tb). METHODS: We screened for microRNA with immune-regulatory functions against M.tb by next generation sequencing of peripheral blood mononuclear cells, followed by validation in an independent cohort. 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 included proteoglycan, HIF-1 signaling, longevity-regulating, central carbon metabolism, and autophagy. We validated miR-431-3p down-regulation and miR-1303 up-regulation accompanied with corresponding changes in their predicted 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/miR-1303 short interfering RNA in THP-1 cells under ESAT-6 stimuli showed that miR-431-3p and miR-1303 were capable to augment and suppress autophagy/apoptosis/phagocytosis of macrophage via targeting MDR1/MMP16/RIPOR2 and ATG5, respectively. CONCLUSIONS: This study provides a proof of concept for microRNA-based host-directed immunotherapy for active TB disease. The combined miR-431-3p over-expression and miR-1303 knock-down revealed new vulnerabilities of treatment-refractory TB disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / MicroARNs Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Infect Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / MicroARNs Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Infect Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido