Objective: Placental microRNAs (miRNAs) have emerged as important post-transcriptional regulators of gene expression, yet their role in Hypertensive disorders of pregnancy (HDP) pathophysiology remains incompletely understood. This study aimed to determine whether differential expression of placental miRNAs can discriminate between varying severities of HDP and elucidate their potential molecular targets and pathways through bioinformatic analysis. Based on preliminary integrative multi omics findings, the specific objectives were to examine the expression profiles of miR-26b-5p and miR-498-5p in preeclampsia (PE), pregnancy induced hypertension (PIH), and healthy pregnancy (HP), and to explore their functional relevance in disease pathogenesis. Design and method: Placental tissues were collected from participants with PE (n=20), PIH (n=40), and HP (n=40). Total miRNA was extracted using microRNA isolation kit, followed by cDNA synthesis. The expression levels of miR-26b-5p and miR-498-5p were quantified using real time qPCR and analyzed by the double delta CT method to find the relative fold change to endogenous control, U6. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminative potential of each miRNA. Bioinformatic analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment, were conducted using the R Studio platform to identify putative molecular targets and signaling networks using multiMiR, clusterProfiler, org.Hs.eg.db, enrichplot and ggplot2 packages. Results: The relative fold change of miR-26b-5p expression was significantly downregulated in PE compared to PIH and HP (p<0.0001). Similarly, miR-498-5p expression was reduced in both PE (p<0.0001) and PIH (p=0.0005) when compared to control. Both miRNAs exhibited negative correlations with systolic/diastolic blood pressure, total protein, and uric acid/creatinine ratio. ROC analysis revealed strong discriminatory performance (AUC=0.96 for miR-26b-5p and AUC=0.845 for miR-498-5p; p<0.001). KEGG and GO enrichment indicated possible involvement of the MAPK signaling pathway for miR-26b-5p and Wnt signaling for miR-498-5p in disease pathogenesis. Conclusions: The significant downregulation and strong diagnostic performance of miR-26b-5p and miR-498-5p suggest their regulatory roles in HDP pathogenesis via MAPK and Wnt signaling pathways, respectively. Further validation of these mechanistic links could aid in development of miRNA based targeted therapies.
Joy et al. (Fri,) studied this question.