MicroRNA-155Is Involved In The Remodelling Of Human-trophoblastderived HTR-8/SVneo Cells Induced By

Objective A low dose injection of lipopolysaccharides (LPS) may induce pre-eclampsia (PE)-like symptoms in rats, and microRNA-155(miR-155) is elevated in the placentas of patients with PE. Our goal was to investigate the association of miR-155with PE and the pathways involved using human-trophoblast-derived HTR-8/SVneo cells stimulated with LPS.Methods We measured miR-155in HTR-8/SVneo cells treated with LPS (25-800ng/ml) using real-time PCR. Western blotting was used to study transcription factor activated protein1(AP-1)(JunB and FosB subunits) and nuclear factor (NF)-kB p65in the HTR-8/SVneo cells and placentas from patients with PE. DNA precipitation assays and luciferase reporter analysis were used to evaluate the regulation of miR-155by AP-1and NF-kB. Cell migration was determined by scratch assay. Syncytialization of HTR-8/SVneo cells was analysed following transfection with miR-155.Results miR-155was increased together with AP-1and NF-kB in HTR-8/SVneo cells incubated with low dose of LPS (≤100ng/ml; P<0.05versus baseline). Both JunB/FosB and p65were increased in placenta from women with severe PE versus a normal pregnancy, with elevated expression of miR-155(P<0.05). For specific DNA-binding sites upstream of BIC/miR-155gene promoter, the AP-1site was more important than the NF-kB site for increasing miR-155in HTR-8/SVneo cells. The cells with enforced expression of miR-155showed a reduced ability to migrate (P<0.05) and an increased number of syncytiotrophoblast-like multinuclear cells (P<0.05).Conclusions LPS may induce remodelling of the human-trophoblast-derived HTR-8/SVneo cells by increasing miR-155, acting in part through the AP-1and NF-kB pathways.