Role of MicroRNAs in Autosomal Dominant Polycystic Kidney Disease: Expression Profiles and Pathway Analysis
DEVI, C.; Ranjan, P.; Mishra, J. K.; Singh, S.; Das, P.
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This study investigates the role of specific microRNAs (miRNAs) in autosomal dominant polycystic kidney disease (ADPKD). Network analysis using Cytoscape 3.10.1 revealed 28 miRNAs that target two or more PKD related genes, while 14 miRNAs interacted with three or more genes. Pathway analysis of these 14 miRNAs, conducted via the miRPath V4.0 tool, utilized various resources such as KEGG, GO terms, Pfam, and MSigDB, highlighting their functional roles in ADPKD. Among these 14 miRNAs, four were prioritized for further analysis based on the higher number of target genes and existing evidence of their expression in blood. These miRNAs were analyzed for fold change expression levels using qRT-PCR on blood-derived RNA samples from ADPKD patients (n=19) and healthy controls (n=5). These four miRNAs--hsa-miR20a-5p, hsa-miR27b-3p, hsa-miR3613-3p, and hsa-miR181a-5p-- showed significant upregulation with p-values of 0.0179, 0.0002, 0.0166, and 0.0402 respectively. The functional enrichment of miRNAs involved in PKD evidently suggests that these play diverse roles in regulating key processes such as cell cycle progression, mTOR signaling, autophagy, EMT, and cellular responses to hypoxia thus playing crucial role in the pathogenesis of ADPKD and could serve as potential biomarkers or therapeutic targets.
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