Background: Sepsis-associated acute kidney injury (S-AKI) is a life-threatening complication of sepsis, characterized by severe renal dysfunction and uncontrolled inflammation. Long non-coding RNAs (lncRNAs) have emerged as critical regulators in S-AKI pathogenesis, yet the role of lncRNA ZEB1-AS1 remains unclear. Methods: This study enrolled sepsis patients categorized into non-AKI (N-AKI) and S-AKI groups, with healthy controls (HC). Serum ZEB1-AS1, miR-625-5p, and RUNX1 levels were quantified by RT-qPCR. Logistic regression and ROC analysis evaluated biomarker diagnostic value. Molecular interactions between ZEB1-AS1, miR-625-5p, and RUNX1 were validated using dual-luciferase reporter assays, RIP, and correlation analysis. In vitro experiments used LPS-stimulated HK-2 cells with siRNA transfection to investigate functional roles. Results: S-AKI patients showed significantly elevated ZEB1-AS1 and reduced miR-625-5p expression compared to N-AKI patients and HC. ZEB1-AS1 achieved an 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 positive correlation with ZEB1-AS1 and negative correlation with miR-625-5p. In LPS-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. Conclusion: 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.
Yu et al. (Tue,) studied this question.