Circ_0015382 is associated with preeclampsia and regulates biological behaviors of trophoblast cells through miR-149-5p/TFPI2 axis.

INTRODUCTION: Circ_0015382 expression was found to be up-regulated in preeclampsia (PE) placenta tissues, while the role and molecular mechanisms of circ_0015382 in PE remain unclear. METHODS: The expression of circ_0015382, microRNA (miR)-149-5p, and tissue factor pathway inhibitor 2 (TFPI2) was measured using quantitative real-time polymerase chain reaction and Western blot. Cell proliferation, migration, invasion, apoptosis, and cell cycle, were detected using cell counting kit-8, transwell, and flow cytometry assays, respectively. The direct interaction between miR-149-5p and circ_0015382 or TFPI2 was analyzed using the dual-luciferase reporter assay. RESULTS: Circ_0015382 was highly expressed in placental tissues of PE. Overexpression of circ_0015382 suppressed trophoblast cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), but induced apoptosis and cell cycle progression, while circ_0015382 knockdown showed inverse effects. MiR-149-5p was confirmed to be a target of circ_0015382, and silencing miR-149-5p reversed the regulatory effects of circ_0015382 knockdown on trophoblast cell biological behaviors. MiR-149-5P was expressed at lower levels in placental tissues of PE, while the expression of its target TFPI2 was higher. Importantly, circ_0015382 could regulate TFPI2 expression via miR-149-5p. Additionally, miR-149-5p was shown to promote trophoblast cell growth, migration, invasion and EMT through TFPI2. DISCUSSION: Circ_0015382 was associated with the onset and development of PE through suppressing trophoblast cell growth, migration, invasion and EMT via miR-149-5p/TFPI2 axis, revealing a new insight into the pathogenesis of PE and a potential therapeutic target for PE treatment.

Vascular endothelial growth factor gene polymorphisms and hypertensive disorder of pregnancy: A meta-analysis.

BACKGROUND: Whether vascular endothelial growth factor (VEGF) polymorphisms affect individual susceptibility to hypertensive disorder of pregnancy remain controversial. Therefore, we performed this meta-analysis to better evaluate associations between VEGF polymorphisms and hypertensive disorder of pregnancy in a larger pooled population. METHODS: Pubmed, Web of Science, Embase and CNKI were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Totally 24 studies were eligible for analyses. In overall analyses, a significant association with hypertensive disorder of pregnancy was observed for rs3025039 polymorphism in dominant (p = 0.01, OR = 0.66, 95%CI 0.48-0.91), recessive (p = 0.002, OR = 1.79, 95%CI 1.25-2.58), overdominant (p = 0.04, OR = 1.35, 95%CI 1.01-1.80) and allele (p = 0.01, OR = 0.72, 95%CI 0.56-0.93) comparisons. But we did not observe any significant associations with hypertensive disorder of pregnancy for other VEGF polymorphisms in overall analyses. Further subgroup analyses by ethnicity showed that rs2010963 polymorphism was significantly associated with hypertensive disorder of pregnancy in Caucasians (dominant and recessive models) and Africans (allele model), whereas rs3025039 polymorphism was significantly associated with hypertensive disorder of pregnancy in Asians (recessive model). CONCLUSIONS: In summary, our findings indicated that rs2010963 and rs3025039 polymorphisms were both significantly associated with the susceptibility to hypertensive disorder of pregnancy in certain populations.