{"title":"The LNCRNA ZEB1-AS1/MIR-625-5P Axis: Diagnostic and Prognostic Potential and Mechanistic Insights in Sepsis-Associated Acute Kidney Injury.","authors":"Xue Yu, Deyu Chen, Fang Liu, Peng Huang","doi":"10.1097/SHK.0000000000002808","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"704-714"},"PeriodicalIF":2.7000,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002808","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍：
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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