Distinct mRNA and long non-coding RNA expression profiles of decidual natural killer cells in patients with early missed abortion
Distinct mRNA and long non-coding RNA expression profiles of decidual natural killer cells in patients with early missed abortion
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早期稽留流产患者蜕膜自然杀伤细胞的独特 mRNA 和长非编码 RNA 表达谱
DOI：
10.1096/fj.202000621r
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发表时间：
2020-09-11
期刊：
影响因子：
4.8
通讯作者：
Liu, Xinmei
中科院分区：
文献类型：
--
作者：
Li, Tong;Li, Xinzhu;Liu, Xinmei
早期非染色体相关性流产（MA）通常与妊娠期间免疫环境的改变有关。人蜕膜自然杀伤细胞（dNK）是孕早期母胎界面中最丰富的淋巴细胞群，是母体免疫耐受的重要调节因子，介导胚胎成功着床和胎盘。先前的研究表明，dNK细胞可能在MA中发挥作用。然而，早期MA患者中dNK细胞的基因表达状态和特异性改变的表现在很大程度上仍然未知。在这里，我们通过RNA测序发现，MA dNK细胞具有不同的mRNA和lncRNA表达谱，与对照组相比，共有276个mRNA和67个lncRNA表达差异。对差异表达mrna进行蛋白-蛋白互作分析，鉴定中心基因和关键模块。构建具有小世界特性的lncRNA-mRNA调控网络，揭示不同枢纽lncrna对mRNA转录的调控。对差异表达的mrna和lncrna进行功能注释，以揭示它们在MA发病机制中的潜在作用。我们的数据强调了几种可能影响MA的丰富的生物过程（免疫反应、炎症反应、细胞粘附和细胞外基质[ECM]组织）和信号通路（细胞因子-细胞因子受体相互作用、ECM受体相互作用、toll样受体信号通路和磷脂酰肌醇信号系统）。这项研究首次证实了mRNA和lncRNA表达谱的改变参与了早期MA的dNK细胞发病机制，有助于更好地理解潜在的分子机制，并开发针对关键mRNA和lncRNA的新型MA治疗策略。
Early non-chromosome-related missed abortion (MA) is commonly associated with an altered immunological environment during pregnancy. Human decidual natural killer (dNK) cells, the most abundant lymphocyte population within the first-trimester maternal-fetal interface, are vital maternal regulators of immune tolerance mediating successful embryo implantation and placentation. Previous studies have shown that dNK cells may play a role in MA. However, the gene expression status and specific altered manifestations of dNK cells in patients with early MA remain largely unknown. Here, we show that MA dNK cells have distinct mRNA and lncRNA expression profiles through RNA sequencing, with a total of 276 mRNAs and 67 lncRNAs being differentially expressed compared with controls. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. An lncRNA-mRNA regulatory network characterized by the small-world property was constructed to reveal the regulation of mRNA transcription by differential hub lncRNAs. Functional annotation of differentially expressed mRNAs and lncRNAs was performed to disclose their potential roles in MA pathogenesis. Our data highlight several enriched biological processes (immune response, inflammatory response, cell adhesion, and extracellular matrix [ECM] organization) and signaling pathways (cytokine-cytokine receptor interaction, ECM-receptor interaction, Toll-like receptor signaling pathway, and phosphatidylinositol signaling system) that may influence MA. This study is the first to demonstrate the involvement of altered mRNA and lncRNA expression profiles in the dNK cell pathogenesis of early MA, facilitating a better understanding of the underlying molecular mechanisms and the development of novel MA therapeutic strategies targeting key mRNAs and lncRNAs.