Abstract
Backgrounds: Rheumatoid arthritis (RA) is a frequent autoimmune disease. Emerging evidence indicated that ZNFX1 antisense RNA1 (ZFAS1) participates in the physiological and pathological processes in RA. However, knowledge of ZFAS1 in RA is limited, the potential work pathway of ZFAS1 needs to be further investigated.Methods: Levels of ZFAS1, microRNA (miR)-2682-5p, and ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to explore the ability of cell proliferation in fibroblast-like synoviocytes (FLS-RA). Cell apoptosis was measured via flow cytometry. Also, levels of ADAMTS9, apoptosis-related proteins, cleaved-caspase-3 (active large subunit), and autophagy-related proteins were identified adopting Western blot. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the productions of inflammatory cytokines. Beside, the interrelation between miR-2682-5p and ZFAS1 or ADAMTS9 was verified utilizing dual-luciferase reporter assay.Results: High levels of ZFAS1 and ADAMTS9, and a low level of miR-2682-5p were observed in RA synovial tissues and FLS-RA. Knockdown of ZFAS1 led to the curbs of cell proliferation, inflammation, autophagy, and boost apoptosis in FLS-RA, while these effects were abolished via regaining miR-2682-5p inhibition. Additionally, the influence of miR-2682-5p on cell phenotypes and inflammatory response were eliminated by ADAMTS9 up-regulation in FLS-RA. Mechanically, ZFAS1 exerted its role through miR-2682-5p/ADAMTS9 axis in RA.Conclusion: ZFAS1/miR-2682-5p/ADAMTS9 axis could modulate the cell behaviors, inflammatory response in FLS-RA, might provide a potential therapeutic target for RA treatment.
Highlights
Rheumatoid arthritis (RA) is one of the most common chronic joint diseases characterized by the aggressive proliferation of synoviocytes, accompanied by the secretions of inflammatory cytokines and chemokines [1]
fibroblast-like synoviocytes (FLSs)-RA and FLS-Normal were segregated from relative synovial tissues, a similar tendency of ZNFX1 antisense RNA1 (ZFAS1) level was discovered in FLS-RA (Figure 1B)
Until now, growing evidence has displayed that Long non-coding RNAs (lncRNAs) worked as various roles in diverse biological regulation, including cell growth, apoptosis, autophagy and inflammatory response [27]
Summary
Rheumatoid arthritis (RA) is one of the most common chronic joint diseases characterized by the aggressive proliferation of synoviocytes, accompanied by the secretions of inflammatory cytokines and chemokines [1]. Long non-coding RNAs (lncRNAs) have attracted mountainous attention for their association with the homeostasis and biological modulation, such as cell growth, apoptosis, inflammatory response, and immunity [7]. LncRNAs consists of more than 200 nucleotides in length, and there is increasing evidence that lncRNAs can be used for numerous inflammatory diseases, including RA [8,9]. LncRNA ZNFX1 antisense RNA1 (ZFAS1) was a cancer-related lncRNA [11,12], it contributed to oncogenesis via sponging microRNA (miRNA/miR)-150-5p in melanoma [13]. Based on the features of ZFAS1 in cell behaviors, we considered whether ZFAS1 could participate in the progression of RA
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