The LNCRNA ZEB1-AS1/MIR-625-5P Axis: Diagnostic and Prognostic Potential and Mechanistic Insights in...

Sepsis-associated acute kidney injury (S-AKI) is a life-threatening complication of sepsis, characterized by severe renal dysfunction and uncontrolled inflammation. Long noncoding RNAs have emerged as critical regulators in S-AKI pathogenesis, yet the role of long noncoding RNA ZEB1-AS1 remains unclear.

This study enrolled sepsis patients categorized into non-AKI and S-AKI groups, with healthy controls. Serum ZEB1-AS1, miR-625-5p, and RUNX1 levels were quantified by real-time quantitative polymerase chain reaction. Logistic regression and receiver operating characteristic analysis evaluated the biomarker diagnostic value. Molecular interactions between ZEB1-AS1, miR-625-5p, and RUNX1 were validated using dual-luciferase reporter assays, RNA immunoprecipitation, and correlation analysis. In vitro experiments used lipopolysaccharide-stimulated HK-2 cells with siRNA transfection to investigate functional roles.

S-AKI patients showed significantly elevated ZEB1-AS1 and reduced miR-625-5p expression compared with non-AKI patients and healthy controls. ZEB1-AS1 achieved an area under the curve (AUC) of 0.824 for diagnosing AKI in sepsis, while miR-625-5p had an AUC of 0.811; their combination improved accuracy (AUC = 0.917). High ZEB1-AS1 or low miR-625-5p levels predicted poor survival in S-AKI patients. Mechanistically, ZEB1-AS1 directly bound miR-625-5p, suppressing its activity. RUNX1, a direct target of miR-625-5p, showed a positive correlation with ZEB1-AS1 and a negative correlation with miR-625-5p. In lipopolysaccharide-treated HK-2 cells, ZEB1-AS1 overexpression exacerbated apoptosis and inflammation, which was reversed by si-ZEB1-AS1-mediated knockdown. Inhibiting miR-625-5p counteracted the protective effects of ZEB1-AS1 knockdown, while RUNX1 silencing restored cell viability.

ZEB1-AS1 and miR-625-5p show promise as diagnostic and prognostic biomarkers for S-AKI. The ZEB1-AS1/miR-625-5p/RUNX1 axis drives tubular injury and inflammation in S-AKI.