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Circ-WDR27 regulates mycobacterial vitality and secretion of inflammatory cytokines in Mycobacterium tuberculosis-infected macrophages via the miR-370-3p/FSTL1 signal network

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Abstract

Tuberculosis (TB) is a common disease caused by Mycobacterium tuberculosis (M.tb) infection. Our study was to explore the function and mechanism of circular RNA WD repeat domain 27 (circ-WDR27) in TB progression. Cell viability and apoptosis were detected by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide assay and flow cytometry. Protein quantification was performed by Western blot. Inflammatory cytokines were examined using enzyme-linked immunosorbent assay. RNA levels were assayed via quantitative reverse-transcription polymerase chain reaction. M.tb survival was assessed using colony-forming unit assay. Target binding was analyzed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Cell damages were induced by M.tb infection, and inflammatory cytokines were secreted in human macrophages. Circ-WDR27 was downregulated in TB patients and M.tb-infected macrophages. Circ-WDR27 overexpression reduced M.tb survival and released inflammatory cytokines in macrophages. Circ-WDR27 acted as a sponge for miR-370-3p. Circ-WDR27-mediated inhibition of TB progression was partly achieved by sponging miR-370-3p. miR-370-3p directly targeted Follistatin-like protein 1 (FSTL1). FSTL1 suppressed M.tb-induced cell damages, and reversed the protective role of miR-370-3p inhibition in TB progression. Circ-WDR27 regulated FSTL1 expression by targeting miR-370-3p. These results showed that circ-WDR27 repressed M.tb vitality and stimulated pro-inflammatory cytokines in M.tb-infected macrophages by affecting the miR-370-3p/FSTL1 axis.

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Funding

This study was supported by the Hunan Provincial Natural Science Foundation of China (No. 2019JJ80044).

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Author notes

  1. Yong Zhang and Danlin Luo contributed equally to this work.

Authors and Affiliations

  1. 6th Medical Department, Hunan Chest Hospital, Changsha, 410013, China

    Yong Zhang, Danlin Luo, Mi Tang & Hengzhong Yi

  2. Department of Ultrasound, The First Affiliated Hospital of University of South China, Hengyang, 421001, China

    Di Jiang

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  1. Yong Zhang
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  2. Danlin Luo
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  3. Mi Tang
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  4. Di Jiang
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  5. Hengzhong Yi
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Correspondence to Hengzhong Yi.

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The authors declare that they have no conflict of interest.

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Corresponding editor: Dipankar Nandi

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Zhang, Y., Luo, D., Tang, M. et al. Circ-WDR27 regulates mycobacterial vitality and secretion of inflammatory cytokines in Mycobacterium tuberculosis-infected macrophages via the miR-370-3p/FSTL1 signal network. J Biosci 47, 28 (2022). https://doi.org/10.1007/s12038-022-00265-8

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  • DOI: https://doi.org/10.1007/s12038-022-00265-8

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