Long non-coding RNA PVT1 can regulate the proliferation and inflammatory responses of rheumatoid arthritis fibroblast-li
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RESEARCH ARTICLE
Long non‑coding RNA PVT1 can regulate the proliferation and inflammatory responses of rheumatoid arthritis fibroblast‑like synoviocytes by targeting microRNA‑145‑5p Jiajun Tang1 · Shiyu Yi1 · Yi Liu1 Received: 22 April 2020 / Accepted: 24 August 2020 © Japan Human Cell Society 2020
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 TNFα-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. Keywords LncRNA PVT1 · Rheumatoid arthritis · miR-145-5p · Fibroblast-like synoviocyte · NF-κb
Introduction Rheumatoid arthritis (RA) is a chronic and autoimmune disease that is characterized by systemic inflammation, pain, joint swelling, articular cartilage destruction, and bone erosion [1]. RA severely affects the health and quality of life of patients [2–5]. Based on the results of previous studies, the lifetime risk of RA is 3.6% for females and 1.7% for males [6, 7]. The pathogenesis of RA remains unclear, and it has been reported that a group of cells that reside in the lining of synovial joints, named fibroblast-like synoviocytes (FLSs), may participate in the pathogenesis of RA [8]. The Jiajun Tang and Shiyu Yi contributed equally to this work. * Yi Liu [email protected] 1
Department of Rheumatology and Immumology, Affiliated Hospital of Southwest Medical University, No 319, Zone 3, Zhongshan Road, Luzhou 646000, China
discovery of RA-FLSs is considered one of the hallmark events for RA [9]. LncRNAs are RNAs with little or no protein-coding capacity with a length of ≥ 200 nucleotides [10] that control the expression of their targets by alternative splicing, epigenetics, small RNA sponging and transcriptional/translational regulation [11]. LncRNAs play a piv
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