Preeclampsia (PE), a pregnancy-specific disorder, is a leading cause of perinatal maternal and fetal mortality and morbidity. Impaired migration and invasion of trophoblastic cells and an imbalanced systemic maternal inflammatory response have been proposed as possible causes of pathogenesis of PE. Comparative analysis of PE-affected placentas and healthy placentas has uncovered differentially expressed long noncoding RNAs, microRNAs, and mRNAs. This study was conducted to investigate the effect of a regulatory network among these RNAs on PE pathogenesis. Long noncoding RNA WDR86-AS1, microRNA miR-10b-3p, and mRNA of protein LITAF were identified by screening of genes in existing databases with aberrant expression in PE-affected placentas and potential mutual interactions as revealed by TargetScan, miRanda, and PicTar analyses. This study identified their expression in PE-affected and healthy placentas by RT-PCR. An in vitro experiment was performed on human trophoblast HTR-8/SVneo cells cultured under normoxic or hypoxic conditions. MiR-10b-3p targets were identified in luciferase reporter assays and RNA pull-down assays. The mouse model of PE was set up using a soluble form of FLT-1 for in vivo testing. Lower levels of miR-10b-3p but higher expression of WDR86-AS1 and LITAF were observed in PE-affected placentas and trophoblast cells under hypoxia. WDR86-AS1 and LITAF mRNA were confirmed as targets of miR-10b-3p. WDR86-AS1 downregulated miR-10b-3p but promoted LITAF expression. Microarray analyses revealed that LITAF controlled the inflammatory responses and migration and proliferation of HTR-8/SVneo cells under hypoxia. Indeed, knockdown of WDR86-AS1 and LITAF or overexpression of miR-10b-3p attenuated the hypoxia-induced inhibition of cellular viability, migration, and invasion. Moreover, miR-10b-3p overexpression attenuated the pathological symptoms caused by soluble FLT-1 in vivo. In summary, the WDR86-AS1/miR-10b-3p/LITAF network is probably involved in PE pathogenesis.

子痫前期（PE）是一种妊娠特异性疾病，是围产期母婴死亡率和发病率的主要原因。滋养层细胞的迁移和侵袭受损以及全身性母体炎症反应失衡已被认为是PE发病机制的可能原因。对PE影响的胎盘和健康胎盘的比较分析发现了差异表达的长非编码RNA，microRNA和mRNA。进行这项研究以研究这些RNA之间的调控网络对PE发病机制的影响。通过在现有数据库中筛选在PE影响的胎盘中异常表达并潜在相互作用的基因，鉴定出长的非编码RNA WDR86-AS1，microRNA miR-10b-3p和LITAF蛋白的mRNA，如TargetScan，miRanda和PicTar分析所揭示。这项研究通过RT-PCR确定了它们在受PE影响的健康胎盘中的表达。一个对在常氧或低氧条件下培养的人滋养层细胞HTR-8 / SVneo细胞进行了体外实验。在荧光素酶报告基因测定和RNA下拉测定中鉴定了MiR-10b-3p靶标。PE的小鼠模型是使用可溶形式的FLT-1建立的，用于体内测试。在缺氧条件下，PE感染的胎盘和滋养细胞中观察到较低水平的miR-10b-3p，但较高的WDR86-AS1和LITAF表达。WDR86-AS1和LITAF证实mRNA为miR-10b-3p的靶标。WDR86-AS1下调miR-10b-3p，但促进LITAF表达。基因芯片分析显示，在缺氧条件下，LITAF控制了HTR-8 / SVneo细胞的炎症反应以及迁移和增殖。实际上，WDR86-AS1和LITAF的敲低或miR-10b-3p的过表达减弱了低氧诱导的细胞活力，迁移和侵袭的抑制。此外，miR-10b-3p的过表达减轻了体内可溶性FLT-1引起的病理症状。总之，WDR86-AS1 / miR-10b-3p / LITAF网络可能与PE的发病机理有关。