Circ_0001714 knockdown alleviates lipopolysaccharide-induced apoptosis and inflammation in renal tubular epithelial cells via miR-129-5p/TRAF6 axis in septic acute kidney injury.

BACKGROUND: Circular RNAs (circRNAs) have been shown to play roles in regulating sepsis. Sepsis is a major cause of acute kidney injury (AKI). Herein, we aimed to investigate the role and mechanism of circ_0001714 in the progression of sepsis-induced AKI. METHODS: Human HK-2 cells were exposed to lipopolysaccharide (LPS) for functional experiments. Quantitative real-time polymerase chain reaction and western blotting were used for expression analysis. Functional experiments were performed by using MTT assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). The binding between miR-129-5p and circ_0001714 or TRAF6 (TNF receptor associated factor 6) was validated using dual-luciferase reporter assay. RESULTS: Circ_0001714 expression was higher in sepsis-AKI patients. HK-2 cells were exposed to LPS to imitate the injury of renal tubular epithelial cells during sepsis-AKI. LPS dose-dependently up-regulated circ_0001714, moreover, circ_0001714 silencing reversed LPS-evoked apoptosis and inflammation in HK-2 cells. Mechanistically, circ_0001714 sequestered miR-129-5p to up-regulate TRAF6 expression, implying the circ_0001714/miR-129-5p/TRAF6 feedback loop. MiR-129-5p was decreased, while TRAF6 was increased in sepsis-AKI patients and LPS-stimulated HK-2 cells. MiR-129-5p re-expression or TRAF6 silencing protected against LPS-induced HK-2 cell apoptosis and inflammation. Additionally, a series of rescue experiments showed that miR-129-5p inhibition reversed the inhibitory action of circ_0001714 knockdown on LPS-induced HK-2 cell injury. Furthermore, TRAF6 overexpression also attenuated the protective effects of miR-129-5p on HK-2 cells under LPS treatment. CONCLUSION: Circ_0001714 silencing might alleviate LPS-induced apoptosis and inflammation via targeting miR-129-5p/TRAF6 axis in HK-2 cells.