Circ_0008440 Inhibits Proliferation and Promotes Apoptosis of Trophoblast Cells through the miR-194-5p/PFKFB2 Axis.

Abstract

Preeclampsia (PE), an idiopathic hypertensive disorder that arises during pregnancy, poses a serious threat to the health of expectant mothers. Human chorionic trophoblast cells (HTR-8/SVneo) are associated with the development of PE. It has been reported that circ_0008440 expression is abnormally increased in the placental tissues of PE patients. However, the function of circ_0008440 within HTR-8/SVneo cells during PE has yet to be fully elucidated. The study used RT-qPCR and western blot assay to evaluate the expression levels of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 2 (PFKFB2), circ_0008440, and miR-942-5p in PE patients. Cells viability was measured using cell counting kit-8 (CCK-8) assay. Cell cycle assay and 5-ethynyl-2'-deoxyuridine (EDU) assay were used to measure cell proliferation. Cell apoptosis was assessed using flow cytometry assay. Western blot assay was used to detect protein expression. Dual-luciferase reporter assay and RNA pull-down assay were used to assess the interactions among circ_0008440, miR-942-5p, and PFKFB2 in HTR-8/SVneo cells. The study showed that the expression levels of circ_0008440 and PFKFB2 were significantly increased, while the expression of miR-942-5p was significantly decreased in the placental tissues of PE patients. Silencing of circ_0008440 promoted proliferation and tube formation and inhibited apoptosis of HTR-8/SVneo cells. In terms of molecular mechanism, miR-942-5p inhibitor or overexpression of PFKFB2 could partially reverse the effects of circ_0008440 silencing on the biological characteristics of HTR-8/SVneo cells. Collectively, circ_0008440 could act as a sponge of miR-942-5p to regulate the expression of PFKFB2, which further inhibited viability and proliferation of HTR-8/SVneo cells and promoted cell apoptosis.