高通量测序技术筛选早发型重度子痫前期合并胎儿生长受限的胎盘差异微小RNA表达谱及信号通路  

Placental microRNAs expression profile and signaling pathways in pregnant woman with early-onset severe preeclampsia and fetal growth restriction by high-throughput sequencing

作　　者：林靓[1] 柳之彦 陈发文 杨茵[1] 辛长征 曹雯 林容[1] 董洁琼 郑晶[1] 吴晓丹[3] LIN Liang;LIU Zhi-yan;CHEN Fa-wen;YANG Yin;XING Chang-zheng;CAO Wen;LIN Rong;DONG Jie-qiong;ZHENG Jing;WU Xiao-dan(Department of Gynaecology and Obstetrics,Shengli Clinical College of Fujian Medical University,Fujian Provincial Jinshan Hospital,Fuzhou Fujian 350008,China;不详)

机构地区：[1]福建医科大学省立临床学院,福建省立金山医院妇产科,福建福州350008 [2]福建省立金山医院检验科 [3]福建医科大学省立临床学院,福建省立金山医院麻醉科

出　　处：《中华高血压杂志》2020年第12期1163-1170,共8页Chinese Journal of Hypertension

基　　金：福建省卫健委中青年骨干人才培养项目(2018-ZQN-22);福建省自然科学基金项目(2020J011066);福建省卫生系统中青年骨干项目(2015-ZQM-ZD-4);福建省立医院“创双高”火石基金项目(2020HSJJ19)。

摘　　要：目的探索早发型重度子痫前期(sPE)合并胎儿生长受限(FGR)胎盘组织的微小RNA(miRNA)差异表达谱及相关信号通路。方法收集早发型sPE合并FGR(n=5)和正常孕妇(n=5)的胎盘组织。采用高通量测序技术筛选胎盘中差异表达的miRNA并进行聚类分析。采用TargetScan和miRDB两个靶基因数据库,对差异的miRNA进行靶基因预测。选取两个数据库交叉的靶基因进行GO和KEGG Pathway富集分析,预测靶基因参与的生物学过程及信号通路。结果与对照组相比,sPE组共筛选出35个显著差异表达的miRNA,其中有19个上调,16个下调。还筛选出4个miRNA簇,包括19q13.42、14q32.31、1p36.33和17p13.1。Gene Ontology富集分析表明,差异miRNA与解剖结构、器官系统发育、RNA转录调控、生物合成和代谢过程有关。KEGG Pathway富集分析显示靶基因可能参与Wnt、Hippo、mTOR、Hedgehog等信号通路。富集评分最高的是Wnt信号通路参与调控胎盘发育、维持滋养细胞谱系稳定。6个目标miRNA上下调的趋势和测序结论基本一致且差异倍数相近(P<0.05)。结论早发型sPE合并FGR的胎盘差异性表达的miRNA主要参与胎盘形成及系统器官发育的信号通路。Objective To investigate the placental microRNA(miRNA)expression profile and signaling pathways in pregnant woman with early-onset severe preeclampsia(sPE)and fetal growth restriction(FGR).Methods A total of 10 cases of placental tissues from pregnant woman with early-onset sPE and FGR(n=5)and normal pregnant woman(n=5)were collected.Placental miRNA expression profile was detected by high-throughput sequencing and cluster analysis was performed.The target genes of miRNA with significant differences were predicted by two databases,including TargetScan and miRDB.The Gene Ontology and KEGG pathway analysis were carried out to predict the biological processes and signaling pathways of target genes consisted in both databases.Results A total of 35 placental miRNA with significantly different expression were identified in pregnant woman with sPE,compared with normal pregnant controls,including 19 up-regulated and 16 down-regulated miRNA.And 4 miRNA clusters were identified,including 19 q13.42,14 q32.31,1 p36.33 and 17 p13.1.Gene ontology analysis showed that the differential miRNA were related to anatomical structure,organ systems development,RNA transcriptional regulation,biosynthesis and metabolic process.KEGG pathway analysis showed that target genes may be involved in Wnt,Hippo,mTOR and Hedgehog signaling pathways.Wnt signaling pathway,with the highest enrichment score,was involved in regulating placental development and stabilizing trophoblast cells.The regulating effect of the six target miRNA was consistent with the conclusion of sequencing and the fold change were similar(P<0.05).Conclusions The placental miRNA with significantly different expression are mainly involved in the signaling pathways of placenta formation and systemic organ development.Our findings provide a theoretical basis for the pathogenesis,diagnosis and treatment of early-onset sPE combined with FGR.

关 键 词：重度子痫前期 胎儿生长受限 微小RNA 靶基因 信号通路 

分 类 号：R714.244[医药卫生—妇产科学] R714.5[医药卫生—临床医学]