BACKGROUND: Preeclampsia (PE) is the major cause of maternal and fetal morbidity and
mortality, affecting 3-8% of all pregnancies around the globe. miRNAs are small, noncoding
RNA molecules, which negatively regulate gene expression. Abnormally expressed miRNAs
contribute to pregnancy complications such as PE. The aim of our study was to find
possible regulatory mechanisms by system biology approaches, which are connected to
the pathogenesis of PE. METHODS: We integrated publicly available miRNA and gene expression
profiles and created a network from the significant miRNA-mRNA pairs with the help
of MAGIA and Cytoscape softwares. Two subnetworks were expanded by adding protein-protein
interactions. Differentially expressed miRNAs were identified for the evaluation of
their regulatory effect. We analyzed the miRNAs and their targets using different
bioinformatics tools and through literature research. RESULTS: Altogether, 52,603
miRNA-mRNA interactions were generated by the MAGIA web tool. The top 250 interactions
were visualized and pairs with q < 0.0001 were analyzed, which included 85 nodes and
80 edges signalizing the connections between 52 regulated genes and 33 miRNAs. A total
of 11 of the regulated genes are PE related and 9 of them were targeted by multiple
miRNAs. A total of 8 miRNAs were associated with PE before, and 13 miRNAs regulated
more than 1 mRNA. Hsa-mir-210 was the highest degree node in the network and its role
in PE is well established. CONCLUSIONS: We identified several miRNA-mRNA regulatory
mechanisms which may contribute to the pathogenesis of PE. Further investigations
are needed to validate these miRNA-mRNA interactions and to enlighten the possibilities
of developing potential therapeutic targets.
