Knockdown of circ_CDYL Contributes to Inhibit Angiotensin II-Induced Podocytes Apoptosis in Membranous Nephropathy via the miR-149-5p/TNFSF11 Pathway.

Circular RNAs (circRNAs) have been verified as vital regulators in various diseases, including membranous nephropathy (MN). Therefore, the role of circ_CDYL in podocyte apoptosis and MN was investigated. The real-time quantitative polymerase chain reaction was performed to measure the expression of circ_CDYL, microRNA-149-5p (miR-149-5p), and tumor necrosis factor superfamily member 11 (TNFSF11) in podocytes. In addition, angiotensin II (Ang II) was used to induce apoptosis of podocytes. The apoptosis-related protein expression was quantified by western blot assay. The apoptosis of podocytes was evaluated by flow cytometry assay. The interaction relationship between miR-149-5p and circ_CDYL or TNFSF11 was confirmed by dual-luciferase reporter assay. Circ_CDYL was significantly overexpressed in MN patients and Ang II-induced podocytes compared with control groups. Importantly, loss-of-functional experiments indicated that knockdown of circ_CDYL protected podocytes from Ang II-induced apoptosis. MiR-149-5p was verified as target of circ_CDYL and negatively correlated with circ_CDYL expression in MN patients. Knockdown of circ_CDYL-mediated effects on Ang II-induced podocyte cells were abolished by silencing miR-149-5p. Besides, the upregulation of miR-149-5p could suppress apoptosis in Ang II-induced podocyte cells by targeting TNFSF11. Under Ang II stimulation, the upregulation of TNFSF11 could increase the expression of TNFSF11 and induce apoptosis in circ_CDYL-silencing podocytes. Our results confirmed that circ_CDYL specifically targeted miR-149-5p/TNFSF11 pathway to regulate Ang II-induced apoptosis in podocytes, which might be useful diagnostic biomarkers in MN.