子痫前期患者胎盘中Lnc RNA表达谱的差异分析

摘要

Objective To analyze the difference in expression profile of long non-coding RNA (lncRNA) in placenta of patients with preeclampsia (PE) and normal pregnant women.Methods Twelve PE patients and 12 normal pregnant women visiting obstetrics department of People''s Hospital of Guangxi Zhuang Autonomous Region were recruited.Expression of lncRNA and mRNA in placenta of 3 PE patients and 3 normal pregnant women was detected using Affymetrix lncRNA microarray technology.GO and Pathway analysis were performed to analyze function distribution of differentially expressed lncRNA.Co-expression network of lncRNA and mRNA was constructed.LncRNA associated with PE was screened.Differentially expressed lncRNAs and mRNAs were further confirmed by quantitative real-time PCR.Results There were 26 lnc RNAs with differential expression greater than 1.5 fold in placenta of PE patients, with 9 up-regulated and 17 down-regulated, among which GSTT1 had most significant up-regulation and ENST00000384564 had most significant down-regulation.A total of 208 mRNAs with differential expression greater than 1.2 fold were found in placenta of PE patients, with 87 up-regulated and 121 down-regulated, among which TREML2 had most significant up-regulation and CYTL1 had most significant down-regulation.GO analysis showed that differentially expressed mRNA was mainly involved in innate immune response, inflammatory response, immune response, coagulation and other biological processes.Pathway analysis showed that differentially expressed mRNA was mainly involved in formation of phagocytosis pathway, Fc receptor mediated phagocytosis pathway, natural killer cell mediated cytotoxicity and other signaling pathways.lncRNAs possibly associated with PE such as NR_038877 and NR_002794 were found by lncRNA-mRNA co-expression network.QRT-PCR verified that ARPC3, PIK3CG, CLEC4M, FCGR1A, CYBB and NCF4 were significantly down-regulated in PE group, and n340778, n342887, n345093, n346352, NR_002794, NR_038877 and NR_039741 were significantly up-regulated in PE group, which were consistent with microarray results.Conclusion Expression profile of lncRNA in placenta of patients with PE is significantly changed, which may be involved in the pathogenesis of preeclampsia.%目的 分析子痫前期患者(PE)和正常妊娠者胎盘组织中长链非编码RNA( lncRNA)表达谱的差异.方法 选取在广西壮族自治区人民医院产科就诊的12 例PE患者和12例正常妊娠者.利用 Affymetrix lncRNA 芯片检测其中3 例PE患者 和3 例正常妊娠者胎盘中lncRNA 和mRNA 表达,GO 及Pathway 分析差异表达的lncRNA 功能分布,构建lncRNA-mRNA 的共表达网络,筛选可能与PE相关lncRNA,并应用qPCR进行芯片结果验证.结果 PE患者胎盘中差异表达大于1.5倍的 lncRNA 共有26 个,其中上调有 9个,表达下调有 17个,其中GSTT1上调最显著,ENST00000384564下调最显著;差异表达超过1.2倍的mRNA有 208 个,其中上调 87个,下调121 个,其中TREML2上调最显著,而CYTL1下调最显著.GO分析显示,差异表达的mRNA主要参与先天免疫反应、炎症响应、免疫响应、凝血等生物学过程;pathway分析显示,差异表达的mRNA主要参与吞噬体形成通路、Fc受体介导的吞噬通路、自然杀伤细胞介导的细胞毒性等信号通路.lncRNA-mRNA共表达网络分析找到了NR_038877、NR_002794等可能与PE发病相关的lncRNAs.qRT-PCR 验证了ARPC3、PIK3CG、CLEC4M、FCGR1A、CYBB、NCF4在PE组显著下调;n340778、n342887、n345093、n346352、NR_002794、NR_038877、NR_039741在PE组显著上调,与芯片结果相一致.结论 子痫前期患者胎盘中lnc RNA表达谱发生显著变化,其可能参与了PE的发病过程.