CircUBXN7 as a prognostic risk biomarker for ARDS modulates LPS-stimulated lung epithelial cell injury and the inflammatory response by competitively binding miR-622.

Summary

In 35 ARDS patients, plasma circUBXN7 was elevated and miR-622 reduced, correlating with severity and mortality, with ROC analyses supporting prognostic utility. In LPS-stimulated lung epithelial cells, circUBXN7 aggravated inflammation and barrier injury by sponging miR-622, whereas circUBXN7 inhibition was protective and effects were reversed by miR-622 modulation.

Key Findings

• Plasma circUBXN7 and IL6ST were elevated, while miR-622 was reduced in ARDS; circUBXN7 was higher and miR-622 lower in severe vs. mild/moderate ARDS.
• Non-survivors showed higher circUBXN7 and IL-1β; ROC analyses supported circUBXN7 and IL-1β as prognostic biomarkers.
• In vitro, LPS increased circUBXN7; circUBXN7 knockdown mitigated inflammation and barrier injury, overexpression worsened them, and effects were reversed by miR-622 modulation, indicating competitive binding (sponging) to miR-622.

Clinical Implications

circUBXN7 could inform prognostic stratification at presentation and motivates development of therapies targeting the circUBXN7–miR-622 axis; clinical adoption awaits multicenter validation.

Limitations

• Single-center, small sample size without external validation; causal inference in patients remains limited.
• Lack of in vivo validation; specific downstream targets in patients need confirmation.

Future Directions

Multicenter validation cohorts, longitudinal kinetics of circUBXN7, in vivo models targeting the circUBXN7–miR-622 axis, and early-phase trials of pathway modulation.