Hsa_circRNA_0045861 promotes renal injury in ureteropelvic junction obstruction via the microRNA-181d-5p/sirtuin 1 signaling axis.

Abstract

BackgroundUreteropelvic junction obstruction (UPJO) is one of the most common causes of hydronephrosis in children. This study explored the effects and the regulatory mechanisms of the circular RNA (circRNA) hsa_circRNA_0045861 (circRNA_0045861) in UPJO.MethodsRNA sequencing was used to identify the differentially expressed circRNAs in UPJO. The effects of circRNA_0045861 on renal cell apoptosis was investigated by flow cytometry and Western blot analysis. Furthermore, we used bioinformatics methods to predict the possible target genes of circRNA_0045861. Fluorescence in-situ hybridization and dual-luciferase reporter assays were performed to validate the target genes of circRNA_0045861. Finally, we evaluated the effects of circRNA_0045861 target gene miR-181d-5p on UPJO-induced renal fibrosis in vivo.ResultsRNA sequencing identified 63 upregulated and 64 downregulated circRNAs in UPJO patients. The expression of circRNA_0045861 was significantly elevated in kidney damage both in vivo and in vitro. Silencing circ_0045861 inhibited transforming growth factor (TGF)-β1-induced apoptosis in vitro in human kidney 2 (HK-2) cells. Furthermore, circ_0045861 was shown to directly interact with the microRNA miR-181d-5p and regulate the expression of sirtuin 1 (SIRT1), thereby promoting the progression of apoptosis and renal injury. In addition, overexpression of miR-181d-5p inhibited cell apoptosis and renal fibrosis in a mouse model through downregulating the SIRT1/p53 pathway.ConclusionsCirc_0045861 may be a novel candidate circRNA in the pathogenesis of UPJO by acting as a pro-apoptotic factor via the miR-181d-5p/SIRT1 axis.