CircPVT1在子痫前期中的表达意义及其对胎盘绒毛外滋养层细胞的功能影响和作用机制

Significance of CircPVT1 Expression in Preeclampsia and Its Effect and Mechanism on Placental Extravillous Trophoblasts

目的探究环状RNA PVT1(circPVT1)在子痫前期(preeclampsia,PE)患者胎盘组织中的表达及临床意义,并探究circPVT1对胎盘绒毛外滋养层(extravillous trophoblasts,EVTs)细胞增殖、迁移和侵袭能力的影响以及其可能的分子机制。方法选取子痫前期(PE组)和健康孕妇(Con组)各30例作为研究对象,qRT-PCR检测2组胎盘组织中circPVT1的表达;CCK-8增殖实验、细胞划痕实验和transwell实验检测circPVT1对EVTs细胞功能的影响;利用生物信息学分析、双荧光素酶报告实验和挽救实验等确定circPVT1在EVTs细胞中潜在的作用机制。结果胎盘组织中circPVT1表达与孕妇收缩压、舒张压和尿蛋白呈负相关(r=-0.630、r=-0.608、r=-0.679,均P<0.01),与孕妇分娩孕周和新生儿出生体重呈正相关(r=0.449、r=0.435,均P<0.01);与Con组胎盘组织相比,circPVT1在PE组胎盘组织中表达量显著下降(P<0.05);过表达circPVT1可促进EVTs的增殖、侵袭和迁移,反之,干扰circPVT1表达后EVTs的增殖、侵袭和迁移能力均降低(均P<0.05);circPVT1可直接与miR-145-5p结合,通过Wnt/β-catenin通路促进EVTs细胞增殖和侵袭。结论circPVT1与子痫前期发生及妊娠结局相关,可能通过调控miR-145-5p/Wnt/β-catenin信号通路促进EVTs细胞增殖、迁移和侵袭,参与子痫前期发生。

Objective To explore the expression and clinical significance of circular RNA plasmacytoma variant translocation 1(circPVT1)in placental tissues of preeclampsia(PE)patients,and to study the effect of circPVT1 on the proliferation,migration and invasion of extravillous trophoblasts(EVTs)and its possible mechanisms.Methods The expression of circPVT1 in placental tissues was detected by qRT-PCR in 30 PE patients(PE group)and 30 healthy pregnant women(Con group).The effects of circPVT1 on EVTs were evaluated by CCK-8,wound healing and transwell assays.Furthermore,bioinformatics analysis,dual-luciferase reporter assay and rescue experiment were conducted to determine the underlying mechanism of action of circPVT1.Results The expression of circPVT1 in placental tissues was negatively correlated with systolic blood pressure,diastolic blood pressure and urinary protein level in pregnant women(r=-0.630,-0.608 and-0.679,respectively;P<0.01),but positively associated with gestational age of delivery and newborn birth weight(r=0.449 and 0.435,respectively;P<0.01).The placental expression of circPVT1 in the PE group was lower than that in the Con group(P<0.05).Furthermore,the proliferation,migration and invasion of EVTs were increased by over-expression of circPVT1,but decreased by inhibition of circPVT1 expression(P<0.05).Mechanistically,circPVT1 directly sponged miR-145-5p,and then promoted the proliferation and invasion of EVTs through Wnt/β-catenin pathway.Conclusion CircPVT1 is associated with preeclampsia and pregnancy outcome.It may promote the proliferation,migration and invasion of EVTs by regulating miR-145-5p/Wnt/β-catenin signaling pathway.