Circ_0058051 Targeted miR‐129‐5P Regulates Autophagy‐Related Gene ATG7 to Promote the Inflammation of Gout

Gout is a common autoinflammatory disease that clinically manifests as recurrent joint redness, swelling, and pain, but the molecular mechanism of recurrent gouty inflammation remains unclear. Circular RNAs (circRNAs) might exert their function by regulating autophagy. Our previous studies revealed that autophagy-related genes (ATGs) are differentially expressed in patients with acute gout. The aim of this study was to investigate the molecular mechanism by which circ_0058051 regulates autophagy as a competitive endogenous RNA (ceRNA) in recurrent gouty inflammation. Real-time quantitative PCR was used to measure the expression of circ_0058051, miR-129-5p, ATG7, LC3, and IL-1β. Western blotting was used to assess the protein levels of ATG7, LC3, and IL-1β. Enzyme-linked immunosorbent assay (ELISA) was used to measure the IL-1β, IL-6, and TNF-α levels. A dual-luciferase reporter assay was used to confirm the interaction between circ_0058051, miR-129-5p, and ATG7. The gout group expressed significantly more circ_0058051 and ATG7 and significantly less miR-129-5p than the HC group. In the 20 paired cases, compared with stable gout cases, the expression of circ_0058051 and ATG7 was significantly greater during a gout attack and even greater in patients with gout recurrence. The significant decrease in miR-129-5p expression was more pronounced in patients with gout recurrence. In the simulation model of gout recurrence in the peripheral blood of intercritical gout patients stimulated with MSU, circ_0058051 peaked 2 h after MSU stimulation, ATG7 peaked 1 h after MSU stimulation, and miR-129-5p expression was lowest 1 h after MSU stimulation. In addition, the expression levels of circ_0058051, ATG7, IL-1β, TNF-α, IL-6, and LC3 significantly increased after THP-1 macrophages were treated with MSU, and the expression of miR-129-5p significantly decreased. In MSU-stimulated THP-1 macrophages, circ_0058051 sponges miR-129-5p to promote the expression of the miR-129-5p target gene ATG7, leading to acute gout attack. Our findings suggest that circ_0058051 is involved in the recurrence of acute gout by targeting miR-129-5p to regulate ATG7-mediated autophagy.