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

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.