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Role of miR-9-5p in preventing peripheral neuropathy in patients with rheumatoid arthritis by targeting REST/miR-132 pathway

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Abstract

MicroRNAs (miRNAs) are found to play a key role in neural cell differentiation, peripheral nerve injury, and rheumatoid arthritis (RA). However, no study has yet been conducted highlighting their role in RA-induced peripheral neuropathy. Here, we investigated the role of miRNAs in RA-induced peripheral neuropathy. Levels of six miRNAs were detected in serum collected from 15 patients with RA and peripheral neuropathy and 16 patients with RA. In vitro, Schwann cells were treated with 0.1 ng/mL IL-6 and 20 ng/mL TNF-α. The expression level of miR-9-5p and its association with the repressor element-1 silencing transcription factor (REST) were investigated. The roles of miR-9-5p and REST in Schwann cell injury were examined after transfection of miR-9-5p mimics or REST siRNA. In patients with RA and peripheral neuropathy, serum miR-9-5p was significantly downregulated when compared with RA. In IL-6- and TNF-α-stimulated Schwann cells, apoptosis was induced, while the cell viability and level of miR-9-5p were inhibited. A significantly negative correlation was observed between miR-9-5p and REST. Transfection of miR-9-5p mimics and REST siRNA significantly reversed the inhibition of cell viability and induction of apoptosis caused by IL-6 and TNF-α. In addition, overexpression of miR-9-5p upregulated the expression of miR-132, miRNA targeting E1A binding protein EP300 (EEP300), phosphatase and tensin homolog (PTEN) and forkhead box O3 (FOXO3). These results showed that Schwann cells were protected by miR-9-5p from inflammatory damage by targeting REST/miR-132 pathway, which could provide new targets for treatment of RA-induced peripheral neuropathy.

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Funding

This work was financially supported by the Linyi Medical Science Development Plan (201515002).

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Authors and Affiliations

  1. Department of Rheumatology, Qilu Hospital of Shandong University, No.107, Wenhua Xi Road, Jinan, 250012, China

    Zunzhong Li & Xingfu Li

  2. Department of Rheumatology and Immunology, Linyi People’s Hospital, Linyi, China

    Zunzhong Li, Yanshan Li, Zhenchun Zhang & Li Jiang

  3. Department of Paediatrics, Women and Children’s Hospital of Linyi City, Linyi, China

    Qinghua Li

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  1. Zunzhong Li
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  2. Yanshan Li
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  3. Qinghua Li
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  4. Zhenchun Zhang
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  5. Li Jiang
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  6. Xingfu Li
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Contributions

ZZ. L. and XF. L. designed the study. ZZ. L., YS. L., and QH. L. performed experiments and collected data. ZZ. L., ZC. Z., and L. J. analyzed and interpreted the data. ZZ. L. and XF. L. wrote the manuscript. All authors have read and approved the final version of this manuscript.

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Correspondence to Xingfu Li.

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All protocols were approved by the Human Ethics Committee of Qilu Hospital of Shandong University.

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The authors declare that they have no conflict of interest.

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Editor: Tetsuji Okamoto

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Li, Z., Li, Y., Li, Q. et al. Role of miR-9-5p in preventing peripheral neuropathy in patients with rheumatoid arthritis by targeting REST/miR-132 pathway. In Vitro Cell.Dev.Biol.-Animal 55, 52–61 (2019). https://doi.org/10.1007/s11626-018-0310-2

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  • DOI: https://doi.org/10.1007/s11626-018-0310-2

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