UCK2 promotes the proliferation,migration, and invasion of trophoblast cells in preeclampsia by activating the STAT3 pathway

Background: Preeclampsia (PE), characterized by hypertension and proteinuria, leads to serious maternal andinfant complications. Uridine-cytidine kinase 2 (UCK2) belongs to the UCK family, a class of enzymes that catalyzes theconversion of uridine and cytidine to monophosphate form. However, the role of UCK2 in PE has not been reported.Methods: The expression of UCK2 was detected in the placenta of PE patients and N(ω)-nitro-L-arginine methyl esterinduced PE mouse model. Through forced up-regulation or down-regulation of UCK2 in vitro, we examined the effects ofUCK2 on the proliferation, apoptosis, migration, and invasion of trophoblast cells. Stattic, the inhibitor of STAT3pathway, was used to investigate whether the STAT3 pathway mediates the biological function of UCK2 introphoblast cells. Results: The present study found that UCK2 showed low expression in the placenta of PE patientsand PE mouse model. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometryassays verified that up-regulation of UCK2 promoted the proliferation of trophoblast cells, while the silence of UCK2suppressed cell proliferation. Besides, flow cytometry and TdT-mediated dUTP Nick-End Labeling assaysdemonstrated that knockdown of UCK2 resulted in apoptosis of trophoblast cells. The wound healing and transwellassays showed that the migration and invasion activities of the trophoblast cells were facilitated by the overexpressionof UCK2 and were blocked by the silence of UCK2. Furthermore, the expression of phosphorylated STAT3 wasincreased with the upregulation of UCK2 and decreased with the inhibition of UCK2. When the STAT3 pathway wasblocked by its inhibitor stattic, the promotion effects of UCK2 on trophoblast cells were suppressed. Conclusion:UCK2 promotes the proliferation, migration, and invasion of trophoblast cells, and these effects may be partlymediated by the activation of the STAT3 pathway.