miR-769-5p has diagnostic value in acute kidney injury in intensive care unit patients and mediates disease development by targeting SIRT6.

Abstract

Background: This investigation was designed to assess the diagnostic value of miR-769-5p in acute renal injury (AKI) among intensive care unit (ICU) patients and explore its mechanism by targeting silent information regulator 6 (SIRT6).

Methods: 80 sepsis patients without AKI and 82 with sepsis-induced AKI (S-AKI) were enrolled. HK-2 cells were induced with lipopolysaccharide (LPS) to construct an in vitro cell model. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to quantify mRNA levels of miR-769-5p, SIRT6, and renal tubular injury markers kidney injury molecule-1 (KIM-1) and Neutrophil gelatinase-associated lipocalin (NGAL). The receiver operating characteristic (ROC) curve was applied to assess miR-769-5p's diagnostic ability for S-AKI. Cell proliferation, apoptosis, inflammatory cytokines, and oxidative stress markers were assessed using CCK-8, flow cytometry, ELISA, and commercial kits, respectively. Finally, RNA immunoprecipitation assay and Dual-luciferase reporter assay confirmed miR-769-5p's direct targeting of SIRT6.

Results: miR-769-5p expression was higher in S-AKI patients compared to Sepsis patients, while SIRT6 was downregulated. miR-769-5p with 87.8% sensitivity and 83.8% specificity, could identify S-AKI patients from Sepsis patients. In HK-2 cells, LPS increased miR-769-5p level and decreased cell viability. Additionally, inhibiting miR-769-5p alleviated LPS-induced cell growth restraint and apoptosis promotion, and the LPS-promoted expression of inflammatory factors, oxidative stress indicators, and tubular injury markers were also weakened by low miR-769-5p expression. miR-769-5p targeted SIRT6, which was downregulated in AKI.

Conclusions: miR-769-5p has diagnostic value in identifying the occurrence of AKI in sepsis patients. Targeted regulation of miR-769-5p may offer a new treatment strategy for AKI.