Cui Liyuan, Shi Minfeng, Meng Xinhang, Qian Jinfeng, Wang Songcun
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200090, China.
State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
Curr Issues Mol Biol. 2023 Oct 31;45(11):8767-8779. doi: 10.3390/cimb45110551.
N6-methyladenosine (m6A) modification is a prevalent modification of messenger ribonucleic acid (mRNA) in eukaryote cells and is closely associated with recurrent pregnancy loss (RPL). Circular RNAs (circRNAs) play critical roles in embryo implantation, trophoblast invasion and immune balance, which are important events during pregnancy. However, how m6A modification is regulated by circRNAs and the potential regulatory mechanism of circRNAs on RPL occurrence remain largely unclassified. We displayed the expression profiles of circRNAs and mRNAs in the decidua of normal pregnancies and RPL patients based on circRNA sequencing and the Gene Expression Omnibus database. A total of 936 differentially expressed circRNAs were identified, including 509 upregulated and 427 downregulated circRNAs. Differentially expressed circRNAs were enriched in immune, metabolism, signaling and other related pathways via the analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The competitive endogenous RNA (ceRNA) network was predicted to supply the possible role of circRNAs in RPL occurrence, and we further analyzed the profiles of nine m6A regulators (seven readers, one writer and one eraser) managed by circRNAs in this network. We also showed the expression profiles of circRNAs in the serum, trying to seek a potential biomarker to help in the diagnosis of RPL. These data imply that circRNAs are involved in pathogenesis of RPL by changing immune activities, metabolism and m6A modification in the ceRNA network. Our study might provide assistance in exploring the pathogenesis and diagnosis of RPL.
N6-甲基腺苷（m6A）修饰是真核细胞中信使核糖核酸（mRNA）的一种普遍修饰，与复发性流产（RPL）密切相关。环状RNA（circRNA）在胚胎着床、滋养层细胞侵袭和免疫平衡中起关键作用，而这些都是孕期的重要事件。然而，circRNA如何调控m6A修饰以及circRNA对RPL发生的潜在调控机制在很大程度上仍未明确。我们基于circRNA测序和基因表达综合数据库展示了正常妊娠和RPL患者蜕膜中circRNA和mRNA的表达谱。共鉴定出936个差异表达的circRNA，其中包括509个上调的和427个下调的circRNA。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，差异表达的circRNA富集于免疫、代谢、信号传导及其他相关通路。预测了竞争性内源性RNA（ceRNA）网络以提供circRNA在RPL发生中的可能作用，并且我们进一步分析了该网络中由circRNA调控的9种m6A调节剂（7种读取器、1种写入器和1种擦除器）的图谱。我们还展示了血清中circRNA的表达谱，试图寻找一种潜在的生物标志物以辅助RPL的诊断。这些数据表明circRNA通过改变ceRNA网络中的免疫活性、代谢和m6A修饰参与RPL的发病机制。我们的研究可能为探索RPL的发病机制和诊断提供帮助。
