An increasing number of data have shown the pathogenesis of preeclampsia (PE) involves circular RNA (circRNA). The study aims to investigate the function and the potential mechanism of circ_0043610 in PE. The study was performed on two human placental trophoblastic cell lines (JEG-3 and HTR-8/SVneo). The expression of circ_0043610, microRNA-558 (miR-558), and RING1 and YY1 binding protein (RYBP) was detected by quantitative real-time polymerase chain reaction. The protein levels of N-cadherin, E-cadherin, and RYBP were assessed by Western blotting. Cell viability, proliferation, apoptosis, invasion, and migration were evaluated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, transwell invasion assay, and wound-healing assay, respectively. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay were performed to identify the associations among circ_0043610, miR-558, and RYBP. Compared with normal placental controls, the increased expression of circ_0043610 and RYBP and the decreased miR-558 expression were detected in PE placental tissues. The overexpression of circ_0043610 led to decreased trophoblast cell proliferation, invasion, and migration but increased cell apoptosis. Mechanistically, circ_0043610 acted as a miR-558 sponge, and miR-558 bound to RYBP. Besides, miR-558 introduction remitted circ_0043610-mediated effects in JEG-3 and HTR-8/SVneo cells. Moreover, RYBP participated in the regulation of miR-558 on trophoblast cell behaviors. Further, the ectopic expression of circ_0043610 led to RYBP upregulation through miR-558. Circ_0043610 induced RYBP production to promote trophoblast dysfunction by binding to miR-558 in PE.
Keywords: Preeclampsia (PE); RING1 and YY1 binding protein (RYBP); circ_0043610; miR-558.