MicroRNA-155 Inhibits Migration And Invasion Of Human Extravillous Trophoblast Devived HTR-8/SV Neo Cells By Down-regulating CD81 Expression

Background:Invasion of trophoblast cells into the uterine spiral arteries is a feature of hemochorial placentation. Insufficient invasion of trophoblast cells is linked to the pathogenesis of preeclampsia (PE). MicroRNA-155 (miR-155) is increased in the placenta of severse PE patients. Cluster of differentiation 81 (CD81) is involved in immune cell activation during inflammation and in tumor cell migration and invasion. This study was conducted to investigate miR-155’s regulation on CD81 expression in trophoblasts and CD81’s effects on trophoblast cell migration and invasion.Methods:The expression of miR-155 and CD81 in PE placenta and lipopolysaccharide (LPS)-injected rat placenta were analyzed by quantitative real-time PCR or Western blot analysis. Luciferase assay was used to analyze the effect of miR-155 on CD81 3’-untranslated region (3’UTR). The effects of CD81 on HTR-8/SVneo cell migration and invasion were examined by scratch assay and transwell invasion assay respectively. Immunofluorescence assay was used to observe p27Kip1 subcellular localization in HTR-8/SVneo cells. The activation of MMP-2 was examined with gelatin zymography.Results:MiR-155 was up-regulated whereas CD81 was down-regulated in PE placenta and LPS-injected rat placenta. MiR-155 inhibited the expression of CD81 in HTR-8/SV neo cells. CD81 promoted the migration and invasion of HTR-8/SVneo cells. Furthermore, over-expression of CD81 could reverse the attenuation of trophoblast cell migration and invasion mediated by miR-155.Conclusions:Our present findings suggest that miR-155 inhibited trophoblast cell migration and invasion by reducing CD81 expression, leading to impaired uterine spiral artery remodeling.