Aberrant expression of imprinted lncRNA MEG8 causes trophoblast dysfunction and abortion

• Published in: Journal of cellular biochemistry Vol. 120; no. 10; pp. 17378 - 17390
• Main Authors: Sheng, Fei, Sun, Ningxia, Ji, Yixuan, Ma, Yan, Ding, Haixia, Zhang, Qing, Yang, Fu, Li, Wen
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2019
• Subjects: Abnormalities; Biological activity; Cell lines; Cell proliferation; Deoxyribonucleic acid; DNA; DNA methylation; DNA microarrays; Embryos; Gene expression; Genomic imprinting; Homology; imprinted lncRNAs; lncRNAs; MEG8; methylation; Miscarriage; Nucleotides; Placenta; placental development; trophoblast; imprinted lncRNAs; lncRNAs; placental development; trophoblast; MEG8; methylation
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.29002

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. In this manuscript, we report the results of the first study on the genetic and functional roles of long noncoding RNA MEG8 on trophoblast cells in early unreasoned miscarriage.