Role of lncRNA BCYRN1 in trophoblast cell physiology and pathogenesis of preeclampsia

Abstract

Long non-coding RNAs (lncRNAs) may play a key role in the pathogenesis of preeclampsia (PE). The present study investigated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in PE. A total of 30 patients with severe PE (SPE) and 30 patients with mild PE (MPE) were recruited, whilst 30 healthy pregnant individuals were enrolled as controls. Placental tissues of enrolled subjects were collected after delivery. The clinical data of pregnant women and newborns were recorded before the correlation between BCYRN1 expression and clinical characteristics was analyzed. Furthermore, HTR-8/SVneo cells were transfected with BCYRN1 overexpression plasmids and BCYRN1 small interfering (si)RNA. Cell Counting Kit-8, Transwell, flow cytometry and tube formation assays were used to detect the function of BCYRN1 in HTR-8/SVneo cells. Reverse transcription-quantitative PCR was used to detect BCYRN1 expression in placental tissues and HTR-8/SVneo cells. Western blotting was used to detect the protein expression levels of Wnt1 and β-catenin. BCYRN1 expression was lower in placenta with mild PE compared with in normal placenta, and was in turn lower in placenta with severe PE. BCYRN1 was negatively correlated with systolic blood pressure and 24-h urinary protein in patients with PE. BCYRN1 siRNA inhibited cell viability, migration, invasion and tube forming abilities whilst increasing apoptosis. By contrast, BCYRN1 overexpression conferred opposite effects. The levels of Wnt1 and β-catenin expression in the cells and placental tissues were next measured. Cells overexpressing BCYRN1 were further treated with the Wnt pathway inhibitor XAV939. Wnt1 and β-catenin expression were elevated when BCYRN1 was overexpressed, but were decreased after BCYRN1 knockdown. XAV939 attenuated the effect of BCYRN1 overexpression on HTR-8/SVneo cells. Overall, the resulted indicated that upregulation of BCYRN1 increased trophoblast viability and prevented apoptosis by activating the Wnt/β-catenin pathway to delay PE onset.