Circ_0000396 inhibits rheumatoid arthritis synovial fibroblast growth and inflammatory response via miR-203/HBP1 axis

• Published in: Journal of biological research (Thessalonikē, Greece) Greece), 2021-01, Vol.28 (1), p.1-11, Article 1
• Main Authors: Wang, Laifang, Zhao, Qing, Wang, Na, Ding, Yanjie, Kong, Lingli, Wang, Jing
• Format: Article
• Language: English
• Subjects: Apoptosis; Arthritis; Assaying; Binding sites; Biomarkers; Cell proliferation; Cholecystokinin; circ_0000396; Colonies; Cytokines; Diagnostic systems; DNA; ELISA; Enzyme-linked immunosorbent assay; Experiments; Fibroblasts; Flow cytometry; Growth; IL-1β; Inflammation; Inflammatory response; Interleukin 6; Interleukin 8; miR-203; HBP1; miRNA; Necrosis; Neoplasms; Nucleotide sequence; Pathogenesis; PCR; Plasmids; Proliferation; Rheumatoid arthritis; Ribonucleic acid; RNA; Software; Synovial fibroblasts; Therapeutic targets; Transcription; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Variance analysis
• ISSN: 2241-5793; 1790-045X; 2241-5793
• DOI: 10.1186/s40709-020-00131-4

Background Circ_0000396 was found to be down-regulated in the rheumatoid arthritis (RA) patients and had a high diagnostic value. However, the function and mechanisms underlying circ_0000396 in RA progression remain unclear. Methods The expression of circ_0000396, microRNA (miR)-203 and HMG-box transcription factor 1 (HBP1) was detected using qRT-PCR and western blot. The proliferative and apoptotic capabilities of rheumatoid arthritis synovial fibroblasts (RASFs) were measured by colony formation, CCK-8, flow cytometry and western blot assays, respectively. The levels of interleukins (IL)-6, IL-1β, IL-8 and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay (ELISA). The target correlations between miR-203 and circ_0000396 or HBP1 were validated using pull-down and dual-luciferase reporter assay. Results Circ_0000396 was decreased in RA synovial tissues and RASFs, and overexpression of circ_0000396 suppressed cell proliferation, induced cell apoptosis and reduced the release of inflammatory cytokine IL-6, IL-1β, IL-8 and TNF-α in RASFs, while circ_0000396 deletion functioned oppositely. MiR-203 was confirmed to be a target of circ_0000396, and miR-203 reversed the protective effects of circ_0000396 on the dysfunction and inflammation of RASFs. HBP1 was a target of miR-203, and silencing miR-203 inhibited RASFs malignant changes by regulating HBP1. In addition, circ_0000396 could regulate HBP1 by sponging miR-203, and HBP1 decrease attenuated the effects of circ_0000396 on RASF growth and inflammation. Conclusion Circ_0000396 inhibited the growth and inflammation in RASFs by regulating miR-203/HBP1 axis, providing a potential therapeutic target for RA.