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

Acute Respiratory Distress Syndrome (ARDS) is a condition involving severe lung injury and respiratory failure that results in high rates of mortality. Although uncontrolled inflammation and alveolar barrier disruption have been reported, the core molecular mechanisms involved in ARDS pathogenesis require clarification. Here, we recruited 35 ARDS patients and investigated the clinical significance of circUBXN7 in ARDS and its molecular mechanism in lipopolysaccharide (LPS)-stimulated acute lung injury. The results revealed that circUBXN7 and IL6ST expression levels were significantly elevated in the plasma of ARDS patients, while miR-622 was downregulated. Plasma circUBXN7 levels were higher and plasma miR-622 levels were lower in patients with severe ARDS, when compared with those with mild and moderate ARDS, whereas IL6ST levels did not significantly differ with disease severity. Furthermore, the non-survivor group exhibited significantly elevated levels of circUBXN7 and IL-1β, when compared with the survivor group. Receiver operating characteristic curve analysis indicated that circUBXN7 and IL-1β may serve as biomarkers for ARDS prognosis. Cellular experiments indicated a significant increase in circUBXN7 levels after LPS treatment. Inhibition of circUBXN7 mitigated the inflammation and cellular barrier damage induced by LPS, whereas its overexpression exacerbated these effects. Additionally, an miR-622 inhibitor or miR-622 mimics significantly reversed the effects of circUBXN7 siRNA or overexpression on cells. These findings demonstrated that circUBXN7 induced an inflammatory response and disrupted barrier integrity by competitively binding to miR-622, thereby impairing its regulatory function on target genes, which provided a novel approach for molecular typing and targeted therapy of ARDS.