Abstract
BackgroundCircular RNAs (circRNAs) are associated with rheumatoid arthritis (RA) development. The purpose of this study is to explore the function and mechanism of circRNA fragile mental retardation 2 (circ-AFF2) in the processes of rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs).MethodsCirc-AFF2, microRNA (miR)-650, and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) levels were determined in synovial tissues of RA and RAFLSs by quantitative reverse transcription polymerase chain reaction or Western blotting. Cell proliferation, inflammatory response, apoptosis, caspase3 activity, migration, invasion, and epithelial-mesenchymal transition (EMT) were investigated using Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), flow cytometry, Transwell, and Western blotting analyses. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and pull-down assays were performed to assess the binding relationship.ResultsCirc-AFF2 expression level was enhanced in synovial tissues of RA and RAFLSs. Circ-AFF2 overexpression facilitated cell proliferation, inflammatory response, migration, invasion, and EMT and repressed apoptosis in RAFLSs. Circ-AFF2 downregulation played an opposite role. Circ-AFF2 targeted miR-650, and miR-650 downregulation reversed the effect of circ-AFF2 interference on RAFLS processes. CNP was targeted by miR-650, and circ-AFF2 increased CNP expression by regulating miR-650. MiR-650 overexpression constrained cell proliferation, inflammatory response, migration, invasion, and EMT and contributed to apoptosis by decreasing CNP in RAFLSs.ConclusionCirc-AFF2 promoted proliferation, inflammatory response, migration, and invasion of RAFLSs by modulating the miR-650/CNP axis.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease with common symptoms like musculoskeletal pain, swelling, and stiffness, which can impair physical function and life quality of patients [1]
Circ-AFF2 level is increased in rheumatoid arthritis (RA) Circ-AFF2 was studied by CircView, which showed that circ-AFF2 was back-spliced by the exon 3 of AFF2 transcripts (Fig. 1a)
To explore whether circ-AFF2 was related to RA development, circ-AFF2 expression change was analyzed in synovial tissues from RA (n = 34) or normal subjects (n = 23)
Summary
Rheumatoid arthritis (RA) is an autoimmune disease with common symptoms like musculoskeletal pain, swelling, and stiffness, which can impair physical function and life quality of patients [1]. Fibroblast-like synoviocytes are the dominant cells of synovial tissues, which contribute to cartilage destruction and RA development by interacting with immune cells and taking part in the inflammatory response of synovial joints [2, 3]. Fibroblast-like synoviocytes have important roles in the onset of RA [4]. Identification of fibroblast-like synoviocyte function in the present study fits into the framework of translational orthopedics by filling the gap between basic sciences and clinical sciences [5, 6]. Illustrating the mechanism of fibroblast-like synoviocyte processes might help to understand RA pathogenesis. The purpose of this study is to explore the function and mechanism of circRNA fragile mental retardation 2 (circ-AFF2) in the processes of rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs)
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