Identification and validation of key non-coding RNAs and mRNAs using co-expression network analysis in pre-eclampsia

Abstract

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.