Data_Sheet_1_H3K4me3-Mediated Upregulation of LncRNA-HEIPP in Preeclampsia Placenta Affects Invasion of Trophoblast Cells.zip

Preeclampsia (PE) is a pregnancy-related disease defined as onset of hypertension and proteinuria after the 20th week of pregnancy, which causes most maternal and perinatal morbidity and mortality. Although placental dysfunction is considered as the main cause of PE, the exact pathogenesis of PE is not yet fully understood. Long non-coding RNAs (lncRNAs) are implicated in a broad range of physiological and pathological processes, including the occurrence of PE. In this study, we investigated the expression and functions of HIF-1α pathway–related lncRNA-HEIPP (high expression in PE placenta) in the pathogenesis of PE. The expression of lncRNA-HEIPP in the placenta from women who underwent PE was screened by lncRNA microarray and then verified using real-time polymerase chain reaction. Then, the methylation profile of the lncRNA-HEIPP promoter and the enrichment of H3K4me3 binding were assessed by bisulfite pyrosequencing and chromatin immunoprecipitation (ChIP)–quantitative polymerase chain reaction (qPCR) assay, respectively. It was found that the level of lncRNA-HEIPP in the PE placenta was significantly higher than that in normal placenta and was increased in HTR-8/SVneo human trophoblast cells upon hypoxia treatment. Moreover, we reported that H3K4me3 manifested significantly higher promoter occupancy on lncRNA-HEIPP promoter in HTR-8/SVneo cells upon hypoxia treatment and found that the downregulation of lncRNA-HEIPP promoted trophoblast invasion. Our findings suggested that the hypoxia-induced expression of lncRNA-HEIPP mediated by H3K4me3 modification in trophoblast may contribute to the pathogenesis of PE.

妊娠期高血压症（PE）是一种与妊娠相关的疾病，其定义为妊娠20周后出现高血压和蛋白尿，导致多数母体和围产期发病率和死亡率升高。尽管胎盘功能障碍被视为PE的主要病因，但PE的确切发病机制尚未完全明了。长非编码RNA（lncRNA）在包括PE发生在内的广泛生理和病理过程中发挥作用。在本研究中，我们探讨了HIF-1α通路相关lncRNA-HEIPP（在PE胎盘中高表达）在PE发病机制中的作用。通过lncRNA微阵列筛选了患有PE的妇女胎盘中lncRNA-HEIPP的表达，并使用实时聚合酶链反应进行验证。随后，通过亚硫酸氢盐测序和染色质免疫沉淀（ChIP）-定量聚合酶链反应（qPCR）试验分别评估了lncRNA-HEIPP启动子的甲基化谱和H3K4me3结合的富集。研究发现，PE胎盘中lncRNA-HEIPP的水平显著高于正常胎盘，并在缺氧处理后在HTR-8/SVneo人滋养层细胞中增加。此外，我们报道了在缺氧处理后，H3K4me3在HTR-8/SVneo细胞中显著提高了lncRNA-HEIPP启动子的结合，并发现lncRNA-HEIPP的下调促进了滋养层侵袭。我们的研究结果表明，由H3K4me3修饰介导的滋养层中lncRNA-HEIPP的缺氧诱导表达可能有助于PE的发病机制。