Identification of lncRNA-miRNA-mRNA networks in late-onset pre-eclampsia

Abstract

Objective: Long non-coding RNAs (lncRNAs) are implicated in multiple pathophysiological processes in placenta-related disorders; however, their expression and function in late-onset pre-eclampsia (LOPE) remain unclear. This study aimed to investigate the expression of lncRNAs in LOPE, construct a competing endogenous RNA (ceRNA) network, and identify the pathways associated with LOPE pathogenesis. Methods: We performed lncRNA and mRNAs microarray profiling to identify the differential expression profiles of lncRNAs and mRNAs in LOPE compared to those in normal pregnancy. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate differentially expressed genes. Subsequently, we generated an interaction network between lncRNAs, (micro-RNAs) miRNAs, and mRNAs based on the Pearson’s correlation coefficient between lncRNAs and mRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to understand the functional significance of differentially expressed lncRNAs (DElncRNAs) in LOPE. Results: We identified 29 DElncRNAs (25 upregulated and four downregulated) and 212 differentially expressed mRNAs (DEmRNAs; 203 upregulated and nine downregulated) in LOPE placentas. Within them, six lncRNAs and four mRNAs were verified by qRT-PCR. GO and KEGG analyses revealed the potential pathways affected by these mRNAs, such as positive regulation of leukocyte chemotaxis, chemokine signaling pathway, and response to hypoxia. Finally, we constructed a ceRNA network including three DElncRNAs and 124 DEmRNAs, whose competing interactions may be mediated by 17 miRNAs. Two DElncRNAs, ENST00000515376 and ENST00000520544, were found to be hub genes, as they interacted with most miRNAs and mRNAs. ENST00000515376 is most likely related to the metabolic process of arachidonic acid, whereas ENST00000520544 is more likely related to the coagulation system, such as the regulation of blood coagulation and platelet degranulation. Conclusion: Differential expression profile of lncRNAs and the lncRNA-miRNA-mRNA network in LOPE provide potential therapeutic targets for this disease.