重度子痫前期差异miRNA和mRNA表达谱的构建与整合分析

Analysis on construction and integration of differential miRNA and mRNA expression profiles of severe preeclampsia

目的探讨重度子痫前期和正常妊娠胎盘组织差异微小RNA(miRNA)及其靶基因在重度子痫前期致病机制中的作用。方法选择剖宫产分娩的重度子痫前期患者和正常妊娠孕妇各5例,应用芯片技术分别检测重度子痫前期和正常妊娠胎盘组织miRNA和mRNA的表达情况,并对差异miRNA和mRNA表达谱进行整合分析,确定在重度子痫前期胎盘组织中差异表达的miRNA的靶基因,并应用生物分子功能注释系统V3.0(MAS V3.0)明确靶基因的生物学功能。结果通过miRNA表达谱芯片筛选出81个差异表达的miRNA,其中80个表达上调,1个表达下调;通过mRNA表达谱芯片筛选出660个差异表达基因,其中256个表达上调,404个表达下调。由于miRNA对其靶基因的负调控作用,通过数据库分析预测及整合分析,得到了56个miRNA靶基因、142个miRNA-靶基因对。这些靶基因涉及离子转运、细胞粘附、血压调节、氧化还原、缺氧反应、炎症反应和信号转导等多方面功能,以及紧密连接、细胞周期、Wnt信号通路、MAPK信号通路、神经活性配体-受体相互作用等多个信号传导通路。结论重度子痫前期患者胎盘组织中差异表达的miRNA及其调控的靶基因可能与重度子痫前期的病及病理生理过程相关。

Objective To identify differentially expressed miRNA and mRNA in placenta of severe preeclampsia cases and normal pregnant women,explore their roles in pathogenesis of preeclampsia.Methods Five severe preeclampsia cases and five normal pregnant women who adopted cesarean section were selected,respectively;chip technology was used to detect the expressions of miRNA and mRNA in placental tissues of severe preeclampsia cases and normal pregnant women;the profiles of differentially expressed miRNA and mRNA were integrated and analyzed,the target genes of differentially expressed miRNA in placental tissues of severe preeclampsia cases were confirmed,biological molecular function annotation system V3.0（ MAS V3.0） was used to confirm biological function of target genes.Results A total of 81 differentially expressed miRNAs were screened out by chip technology,including 80 up-regulated miRNAs and 1 down-regulated miRNA;660 differentially expressed genes were screened out,including 256 up-regulated genes and 404 down-regulated genes.Through database analysis prediction and integrated analysis,56 miRNA target genes and 142 miRNA-target gene pairs were obtained because of the negative regulation function of miRNA to the target gene.The target genes were correlated with multi-function（ ion transport,cell adhesion,blood pressure regulation,oxidation-reduction,response to hypoxia,inflammation reaction,and signal transduction,tight junction,cell cycle） and multiple signal transduction pathways（ Wnt signaling pathway,MAPK signaling pathway and neuroactive ligand-receptor interaction）.Conclusion The differential expressed miRNA and target genes in placental tissues of severe preeclampsia cases may be correlated with pathogenesis and pathophysiological processes of severe preeclampsia.