Changzheng Hospital, Reproductive Medicine Center, Shanghai, China.
Shanghai Changzheng Hospital, Second Military Medical University, Department of Reproductive Medicine Center, Shanghai, China.
J Cell Biochem. 2019 Oct;120(10):17378-17390. doi: 10.1002/jcb.29002. Epub 2019 Jul 2.
Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs whose nucleotides are longer than 200 bp. Previous studies have shown that they play an important regulatory role in many developmental processes and biological pathways. However, the contributions of lncRNAs to placental development are largely unknown. Here, our study aimed to investigate the lncRNA expression signatures in placental development by performing a microarray lncRNA screen. Placental samples were obtained from pregnant C57BL/6 female mice at three key developmental time points (embryonic day E7.5, E13.5, and E19.5). Microarrays were used to analyze the differential expression of lncRNAs during placental development. In addition to the genomic imprinting region and the dynamic DNA methylation status during placental development, we screened imprinted lncRNAs whose expression was controlled by DNA methylation during placental development. We found that the imprinted lncRNA Rian may play an important role during placental development. Its homologous sequence lncRNA MEG8 (RIAN) was abnormally highly expressed in human spontaneous abortion villi. Upregulation of MEG8 expression in trophoblast cell lines decreased cell proliferation and invasion, whereas downregulation of MEG8 expression had the opposite effect. Furthermore, DNA methylation results showed that the methylation of the MEG8 promoter region was increased in spontaneous abortion villi. There was dynamic spatiotemporal expression of imprinted lncRNAs during placental development. The imprinted lncRNA MEG8 is involved in the regulation of early trophoblast cell function. Promoter methylation abnormalities can cause trophoblastic cell defects, which may be one of the factors that occurs in early unexplained spontaneous abortion.
长链非编码 RNA（lncRNA）是一组核苷酸长度大于 200bp 的非编码 RNA。先前的研究表明，它们在许多发育过程和生物途径中发挥着重要的调控作用。然而，lncRNA 对胎盘发育的贡献在很大程度上是未知的。在这里，我们通过进行微阵列 lncRNA 筛选来研究胎盘发育中的 lncRNA 表达特征。从妊娠 C57BL/6 雌性小鼠的三个关键发育时间点（胚胎日 E7.5、E13.5 和 E19.5）获得胎盘样本。微阵列用于分析胎盘发育过程中 lncRNA 的差异表达。除了基因组印迹区域和胎盘发育过程中的动态 DNA 甲基化状态外，我们还筛选了印迹 lncRNA，其表达受胎盘发育过程中 DNA 甲基化的控制。我们发现印迹 lncRNA Rian 在胎盘发育过程中可能发挥重要作用。其同源序列 lncRNA MEG8（RIAN）在人类自然流产绒毛中异常高表达。滋养层细胞系中 MEG8 表达的上调降低了细胞增殖和侵袭，而 MEG8 表达的下调则产生相反的效果。此外，DNA 甲基化结果表明，自发性流产绒毛中 MEG8 启动子区域的甲基化增加。在胎盘发育过程中存在印迹 lncRNA 的动态时空表达。印迹 lncRNA MEG8 参与调节早期滋养层细胞功能。启动子甲基化异常可导致滋养层细胞缺陷，这可能是早期不明原因自然流产发生的因素之一。
