Pre-eclampsia intronic polyadenylation enriched in VEGFA-VEGFR2 signaling pathway

Abstract

Aims: This study aims to reveal transcriptome-wide intronic polyadenylation (IPA) events associated with Pre-eclampsia (PE). Background: Pre-eclampsia (PE) is a potentially life-threatening complication of pregnancy, affecting both maternal and fetal health. However, our understanding of the underlying molecular mechanisms of PE remains limited. Objective: In this study, we conducted a transcriptome-wide analysis of gene expression levels and intronic polyadenylation (IPA) events in samples of patients with PE. We also conducted motif analysis and scanned the microRNA targeting IPA network. Method: We collected 90 PE-related samples from GEO database. IPA events were analyzed using IPAfinder software from hg38 alignment files from STAR. Miranda software was used to perform miRNA target gene prediction. Differentially expressed genes (DEG) were evaluated using edgeR with log2 fold change >1 and adjusted p-value <0.05. Function enrichment was performed through Clusterprofiler. Result: Our analysis revealed that genes in the VEGFA-VEGFR2 signaling pathway were functionally enriched with IPA events related to PE. We observed a negative correlation between gene expression levels and IPA events in VEGFA-VEGFR2 pathway. We identified LIN28B and AGO2 as the most significantly binding motifs to IPA sites. Furthermore, our analysis of miRNA binding sites associated with these IPA events revealed the central regulatory roles of miR-193b and miR-365a in IPA genes. Conclusion: Our findings suggest that transcriptome data-mining might be a useful approach in future studies aimed at identifying potential biomarkers for PE.

Keywords

• Pre-eclampsia
• Transcriptome
• Intronic polyadenylation (IPA)
• VEGFA-VEGFR2 signaling pathway