Circular RNA circ_0111277 Serves as ceRNA, Targeting the miR-424-5p/NFAT5 Axis to Regulate the Proliferation, Migration, and Invasion of Trophoblast Cells in Preeclampsia

Preeclampsia is the main reason for maternal and fetal deaths during the second half of pregnancy. Trophoblast cells play a pivotal role in preeclampsia progression. Circular RNA (circRNA) circ_0111277 has been reported to be related to the development of trophoblast cells. This study is designed to explore the role and mechanism of circ_0111277 on trophoblast cell behavior in preeclampsia. Circ_0111277, microRNA-424-5p (miR-424-5p), and nuclear factor of activated T-cell 5 (NFAT5) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, migration, invasion, and angiogenesis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, tube formation assay, and wound healing assay. Protein levels of matrix metallopeptidase 2 (MMP2), vascular endothelial growth factor-A (VEGF-A), NFAT5, phospho-phosphatidylinositol 3 kinase (p-PI3K), PI3K, phospho-protein kinase B (p-AKT), and AKT were examined by western blot assay. The binding relationship between miR-424-5p and circ_0111277 or NFAT5 was predicted by circBank or starBase and then verified by a dual-luciferase reporter assay. Circ_0111277 and NFAT5 expression were increased in placenta tissues of preeclampsia patients, and miR-424-5p was decreased. Moreover, circ_0111277 knockdown could boost cell viability, migration, invasion, and angiogenesis in trophoblast cells. The mechanical analysis discovered that circ_0111277 acted as a sponge of miR-424-5p to regulate NFAT5 expression. Besides, circ_0111277 silencing promoted the PI3K/AKT signaling pathway in trophoblast cells. Circ_0111277 downregulation could facilitate cell growth and metastasis in trophoblast cells partly by regulating the miR-424-5p/NFAT5 axis, providing an underlying circRNA-targeted therapy for preeclampsia.