Department of Obstetrics and Gynecology, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, Shanxi.
Department of Obstetrics and Gynecology, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Medicine (Baltimore). 2021 Apr 9;100(14):e25294. doi: 10.1097/MD.0000000000025294.
Pre-eclampsia (PE) is a common complication of pregnancy, associated with maternal and fetal morbidity and mortality. In this study, we aimed to explore important long non-coding RNAs (lncRNAs) and their possible mechanisms in PE.GSE60438 expression profile including 25 PE samples and 23 normal samples were obtained from gene expression omnibus (GEO) database. After normalization with betaqn package in R, differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified using the limma package. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway were analyzed using DAVID 6.7 and GSEA 3.0. LncRNAs-mRNAs coexpression was implemented using weighted gene co-expression network analysis (WGCNA). MicroRNAs linked with these DElncRNAs and DEmRNAs were predicted and a competitive endogenous RNA (ceRNA) network was built.A total of 53 DElncRNAs and 301 DEmRNAs were identified between control and PE samples. These DEmRNAs were enriched into pathways such as protein digestion and absorption, osteoclast differentiation. WGCNA constructed a lncRNA-mRNA coexpression network, among which SUMO1P3, NACAP1, NCF1C, ANXA2P1, GTF2IP1, NAPSB, OR7E37P were hub genes. ceRNA network was constructed together with microRNAs (miRNAs), and functional analysis indicated cellular membrane and sugar binding were involved in PE progression. Five lncRNAsANXA2P1, GTF2IP1, NACAP1, NCF1C and OR7E37P were successfully validated in our clinical specimens.The DElncRNAs, including ANXA2P1, GTF2IP1, NACAP1, NCF1C and OR7E37P might play important roles in PE. However, the exact mechanism of these lncRNAs in prediction and diagnosis of PE should be further explored.
子痫前期(PE)是一种常见的妊娠并发症,与母婴发病率和死亡率有关。本研究旨在探讨重要的长非编码 RNA(lncRNA)及其在 PE 中的可能机制。从基因表达综合数据库(GEO)数据库中获得了包括 25 例 PE 样本和 23 例正常样本的 GSE60438 表达谱。在 R 中的 betaqn 包中进行归一化后,使用 limma 包鉴定差异表达的 lncRNA(DElncRNA)和 mRNA(DEmRNA)。使用 DAVID 6.7 和 GSEA 3.0 分析基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径。使用加权基因共表达网络分析(WGCNA)实现 lncRNA-mRNA 共表达。预测与这些 DElncRNA 和 DEmRNA 相关的 microRNAs,并构建竞争性内源 RNA(ceRNA)网络。
在对照和 PE 样本之间共鉴定出 53 个 DElncRNA 和 301 个 DEmRNA。这些 DEmRNA 富集到蛋白消化吸收、破骨细胞分化等途径中。WGCNA 构建了一个 lncRNA-mRNA 共表达网络,其中 SUMO1P3、NACAP1、NCF1C、ANXA2P1、GTF2IP1、NAPSB、OR7E37P 是枢纽基因。与 microRNAs(miRNAs)共同构建了 ceRNA 网络,功能分析表明细胞内膜和糖结合参与了 PE 的进展。在我们的临床标本中成功验证了 5 个 lncRNA:ANXA2P1、GTF2IP1、NACAP1、NCF1C 和 OR7E37P。
包括 ANXA2P1、GTF2IP1、NACAP1、NCF1C 和 OR7E37P 在内的 DElncRNA 可能在 PE 中发挥重要作用。然而,这些 lncRNA 在预测和诊断 PE 中的确切机制仍需进一步探讨。