Distinct mRNA and Long Non-coding RNAs (lncRNAs) Expression Profiles of Decidual Natural Killer Cells in Human Early Missed Abortion. Distinct mRNA and Long Non-coding RNAs (lncRNAs) Expression Profiles of Decidual Natural Killer Cells in Human Early Missed Abortion

Our present study analyzes decidual natural killer(dNK) cells expression profiles of the lncRNA and mRNA in missed abortional patients. A total of 276 mRNAs and 67 lncRNAs were identified to be significantly dysregulated in missed abortion (p<0.01). Subsequently, the potential function of dysregulated mRNAs and lncRNAs in missed abortion were explored through the bioinformatics method. In addition, the relationship between these dysregulated lncRNAs and mRNAs was revealed through constructing the lncRNA-mRNA interaction network. Our data showed that upregulated mRNAs were enriched in immune response and cytokine-cytokine receptor interaction while downregulated mRNAs were mainly related to cell adhesion and ECM-receptor interaction. Most importantly, several novel lncRNAs in dNKs, regulating core maternal-fetal interface activation-related mRNAs, were algorithmically predicted, indicating involvement of lncRNAs in the pathogenesis in early missed abortion.Topology analysis of lncRNA-mRNA interaction network suggested that the network presented a small world property, which means that most of mRNAs in the network were regulated by relative small number of hub lncRNAs. This study paves the way of investigating pathogenesis of early human missed abortion and facilitating the development of novel missed abortion therapeutics targeting lncRNAs. Overall design: RNA sequencing of dNK cells derived from three patients with missed abortion and the other three healthy control women undergoing elective abortions were performed to determine the expression profiles of mRNAs and lncRNAs with poly-A tails.

本研究分析了稽留流产患者蜕膜自然杀伤（decidual natural killer, dNK）细胞的长链非编码RNA（long non-coding RNA, lncRNA）与信使RNA（messenger RNA, mRNA）表达谱。本研究共鉴定出276个mRNA及67个lncRNA在稽留流产患者体内呈现显著表达异常（p<0.01）。随后，通过生物信息学方法探究了异常表达的mRNA与lncRNA在稽留流产中的潜在功能。此外，通过构建lncRNA-mRNA互作网络，揭示了上述异常表达的lncRNA与mRNA之间的调控关系。本研究数据显示，上调表达的mRNA富集于免疫应答及细胞因子-细胞因子受体相互作用通路，而下调表达的mRNA主要与细胞黏附及细胞外基质-受体相互作用相关。尤为关键的是，通过算法预测出dNK细胞中数种新型lncRNA，其可调控母胎界面活化相关的核心mRNA，提示lncRNA参与早期稽留流产的发病机制。对lncRNA-mRNA互作网络的拓扑结构分析表明，该网络呈现小世界特性，即网络内绝大多数mRNA由数量相对较少的枢纽lncRNA调控。本研究为探究人类早期稽留流产的发病机制以及开发以lncRNA为靶点的新型稽留流产治疗手段奠定了基础。整体实验设计：对3名稽留流产患者及3名接受选择性流产的健康对照女性的dNK细胞进行RNA测序，以鉴定带有poly-A尾的mRNA与lncRNA的表达谱。