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

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.