Hsa_circ_0010957 knockdown attenuates lipopolysaccharide-induced HK2 cell injury by regulating the miR-1224-5p/IRAK1 axis

Abstract

Circular RNAs (circRNAs) are involved in the progression of various diseases, including lupus nephritis. Hsa_circ_0010957 is reported to be dysregulated in lupus nephritis, but the exact function of this circRNA is unknown. This research aims to study the function and mechanism of circRNA hsa_circ_0010957 in a lipopolysaccharide (LPS)-induced cellular model of lupus nephritis. Human renal proximal tubular cell line HK2 cells were challenged by LPS. Hsa_circ_0010957, microRNA-1224-5p (miR-1224-5p), and interleukin-1 receptor-associated kinase 1 (IRAK1) abundances were examined by quantitative reverse transcription polymerase chain reaction or western blot. LPS-induced damage was evaluated via cell viability, apoptosis, inflammatory response and oxidative injury. The target interaction was analyzed by dual-luciferase reporter analysis and RNA immunoprecipitation. Hsa_circ_0010957 abundance was enhanced in LPS-challenged HK2 cells. Hsa_circ_0010957 knockdown alleviated LPS-induced apoptosis, the inflammatory response and oxidative injury in HK2 cells. MiR-1224-5p was targeted by hsa_circ_0010957, and miR-1224-5p knockdown reversed the influence of hsa_circ_0010957 silence on LPS-induced injury. IRAK1 was targeted via miR-1224-5p, and hsa_circ_0010957 could regulate IRAK1 by miR-1224-5p. MiR-1224-5p overexpression could mitigate LPS-induced apoptosis, the inflammatory response and oxidative injury, and this effect was abolished by IRAK1. Hsa_circ_0010957 silence weakened LPS-induced HK2 cell apoptosis, the inflammatory response and oxidative injury via regulating the miR-1224-5p/IRAK1 axis.

Keywords

• lupus nephritis
• lipopolysaccharide
• hsa_circ_0010957
• mir-1224-5p
• irak1.