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Long non-coding RNA PVT1 can regulate the proliferation and inflammatory responses of rheumatoid arthritis fibroblast-like synoviocytes by targeting microRNA-145-5p

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Abstract

Long non-coding RNAs (lncRNAs) function in rheumatoid arthritis (RA). The present work was designed to explore the roles of lncRNA PVT1 in RA and the related mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine mRNA level. The binding sites between PVT1 and miR-145-5p were verified by a dual-luciferase reporter assay. Furthermore, RA-FLSs were treated with TNF-α to establish the RA model. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-ethynyl-2′-deoxyuridine (EdU) assays were performed to detect cell proliferation. Flow cytometry and TUNEL assays were performed to detect cell apoptosis. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of inflammatory cytokines. PVT1 was significantly increased and miR-145-5p was decreased in synovial tissues of RA patients. miR-145-5p is a target miRNA of PVT1, and the levels of PVT1 and miR-145-5p in synovial tissues of RA patients were negatively correlated. In RA-FLSs, tumour necrosis factor-α (TNF-α) led to increased PVT1 levels and decreased miR-145-5p levels. Knockdown of PVT1 inhibited TNF-α-induced RA-FLS over-proliferation and reversed TNF-α-induced RA-FLS apoptosis reduction. Moreover, knockdown of PVT1 inhibited TNF-α-induced production of interleukin (IL)‐1β and IL‐6 and the activation of NF-κB through miR-145-5p. PVT1 can regulate apoptosis and inflammatory responses in RA-FLSs by targeting miR-145-5p.

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Author notes

  1. Jiajun Tang and Shiyu Yi contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Immumology, Affiliated Hospital of Southwest Medical University, No 319, Zone 3, Zhongshan Road, Luzhou, 646000, China

    Jiajun Tang, Shiyu Yi & Yi Liu

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  1. Jiajun Tang
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  2. Shiyu Yi
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Correspondence to Yi Liu.

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All patients signed informed consent documents, and this study was approved by the ethical committee of Clinical Medical College, Southwest Medical University [2017(SMU)034].

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Tang, J., Yi, S. & Liu, Y. Long non-coding RNA PVT1 can regulate the proliferation and inflammatory responses of rheumatoid arthritis fibroblast-like synoviocytes by targeting microRNA-145-5p. Human Cell 33, 1081–1090 (2020). https://doi.org/10.1007/s13577-020-00419-6

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  • DOI: https://doi.org/10.1007/s13577-020-00419-6

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