Increasing evidences indicate that circular RNAs (circRNAs) play important roles in regulating gene expressions in various diseases. However, the role of circRNAs in inflammatory response of gouty arthritis remains unknown. This study aims to investigate the role and underlying mechanism of circHIPK3 in inflammatory response of gouty arthritis. Quantitative real-time PCR was used to detect the expressions of circHIPK3, miR-192 and miR-561. Western blot was used to detect the protein levels of TLR4, NLRP3, nuclear factor-κB (NF-κB) related proteins, and Caspase-1. Dual luciferase reporter assay, RNA pull-down assay, and FISH assay were used to confirm the interaction between circHIPK3 and miR-192/miR-561. ELISA was used to detect interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels. circHIPK3 was elevated in synovial fluid mononuclear cells (SFMCs) from patients with gouty arthritis and monosodium urate (MSU)-stimulated THP-1 cells. circHIPK3 overexpression promoted the inflammatory cytokines levels in MSU-stimulated THP-1 cells, and circHIPK3 silencing obtained the opposite effect. Mechanistically, circHIPK3 sponged miR-192 and miR-561, and subsequently promoted the expressions of miR-192 and miR-561 target gene TLR4 and NLRP3. In vivo experiments confirmed circHIPK3 knockdown suppressed gouty arthritis. circHIPK3 sponges miR-192 and miR-561 to promote TLR4 and NLRP3 expressions, thereby promoting inflammatory response in gouty arthritis.

越来越多的证据表明，环状 RNA（circRNA）在调节各种疾病的基因表达中发挥着重要作用。然而，circRNA在痛风性关节炎炎症反应中的作用仍然未知。本研究旨在探讨circHIPK3在痛风性关节炎炎症反应中的作用及其潜在机制。采用实时定量 PCR 检测 circHIPK3、miR-192 和 miR-561 的表达。Western印迹用于检测TLR4、NLRP3、核因子-κB（NF-κB）相关蛋白和Caspase-1的蛋白水平。双荧光素酶报告基因分析、RNA pull-down 分析和 FISH 分析用于确认 circHIPK3 和 miR-192/miR-561 之间的相互作用。ELISA用于检测白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α水平。来自痛风性关节炎患者的滑液单核细胞 (SFMC) 和单钠尿酸盐 (MSU) 刺激的 THP-1 细胞中的 circHIPK3 升高。circHIPK3 过表达促进了 MSU 刺激的 THP-1 细胞中的炎性细胞因子水平，而 circHIPK3 沉默获得了相反的效果。机制上，circHIPK3 海绵化了 miR-192 和 miR-561，随后促进了 miR-192 和 miR-561 靶基因 TLR4 和 NLRP3 的表达。体内实验证实 circHIPK3 敲低抑制了痛风性关节炎。circHIPK3 海绵 miR-192 和 miR-561 促进 TLR4 和 NLRP3 表达，从而促进痛风性关节炎的炎症反应。