CircHIPK3 is decreased in preeclampsia and affects migration, invasion, proliferation, and tube formation of human trophoblast cells

Introduction: The migration and invasion of trophoblast cells into the endometrium and vasculature is a key step in human placentation. Preeclampsia, a devastating multi-system syndrome, is featured by shallow trophoblast invasion and unconverted narrow spiral arteries. Although the alteration in circHIPK3 expression is proved to regulate the invasion and metastasis of various malignant cells, its role in preeclampsia is unknown. Therefore, the aim of this study is to investigate the expression pattern of circHIPK3 in preeclampsia and its impact on trophoblast behavior. Methods: The expression of circHIPK3 in placental tissues obtained from 70 women with preeclampsia and 43 healthy pregnancy controls using quantitative real-time PCR. Clinical information of participants was collected. The effects of circHIPK3 on trophoblast migration, invasion, proliferation, tube formation, and apoptosis were examined in trophoblast cell lines (HTR-8/SVneo) by transfected with knockdown siRNA and overexpression plasmid. Sanger sequencing was performed to verify circHIPK3 in placenta and HTR8/SVneo cells. Results: Significantly decreased circHIPK3 levels were detected in preeclampsia compared with healthy pregnancy controls. The migration, invasion, proliferation, and tube formation capacities of HTR8/SVneo cells were inhibited via circHIPK3 silencing, but circHIPK3 overexpression effectively promotes these capacities except proliferation. No significant difference was observed in apoptosis between cells transfected with siRNA and overexpression plasmid. Discussion: Our findings suggest for the first time that abnormal expression of circHIPK3 may contribute to the development of preeclampsia by leading to the aberrant biological behavior of trophoblast cells. The underlying mechanisms need further study.