LINC00861 protects against sepsis-associated acute kidney injury by regulating apoptosis and inflammation via miR-151a-3p/PDHA1 Axis.

INTRODUCTION AND OBJECTIVE: Sepsis-associated acute kidney injury (SA-AKI) is a critical complication of sepsis marked by high morbidity and mortality. The aim of the study is to investigate the role of LINC00861 and its downstream regulatory axis in SA-AKI. MATERIAL AND METHODS: 220 SA-AKI patients were enrolled and stratified according to survival outcomes. The levels of LINC00861, miR-151a-3p, and PDHA1 were detected in peripheral blood, and correlations with clinical parameters and prognosis were analyzed. In vitro, HK-2 cells were subjected to LPS to establish an SA-AKI model. Functional assays, including flow cytometry, ELISA, and qRT-PCR, were performed to evaluate apoptosis and inflammatory cytokines (IL-6, IL-18, TNF-α). Dual-luciferase assays and rescue experiments were conducted to elucidate the regulatory relationship among LINC00861, miR-151a-3p, and PDHA1. RESULTS: LINC00861 expression was reduced in SA-AKI non-survivor patients and was associated with higher SOFA and APACHE II scores, elevated PCT, SCr, and lactate levels. ROC analysis demonstrated good diagnostic performance (AUC = 0.835). LINC00861 (HR = 0.31, 95% CI: 0.16-0.58) was recognized as an independent prognostic factor for SA-AKI. Overexpression of LINC00861 suppressed LPS-induced apoptosis and reduced pro-inflammatory cytokine release in HK-2 cells. LINC00861 functioned as a sponge for miR-151a-3p, showing a negative correlation. miR-151a-3p directly targeted PDHA1, which was downregulated in non-survivors and positively correlated with LINC00861. Mechanistic analyses revealed that LINC00861 manages apoptosis and inflammation response by the miR-151a-3p/PDHA1 axis. CONCLUSIONS: Reduced LINC00861 was independently associated with poor prognosis in SA-AKI. In vitro, LINC00861 was shown to regulate apoptosis and inflammation through the miR-151a-3p/PDHA1 axis.