Bioinformatics strategy for Determination of microRNAs and Genes Involved in Pathogenesis of Aneurysm in Patient with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in polycystic kidney disease-1 (PKD-1) and PKD-2 genes. The products of these genes, polycysin-1 (PC-1) and PC-2 are expressed as a mechanosensor in the surface of epithelial and endothelial cells, as well as vascular smooth muscle cells (VSMCs). Although cysts in kidneys are common symptoms for diagnosis, cardiovascular problems and cerebral and aortic aneurysms are the main reasons for sudden death in patients. In this study, using bioinformatics approaches, critical genes, microRNAs (miRNAs), and pathways involved in the pathogenesis of aneurysm in ADPKD were investigated.Methods: For microarray analysis, the GSE74451 dataset was downloaded from the GEO NCBI database. The quality of the dataset was assayed by principal component analysis (PCA) using R software. Using the NetworkAnalyst database, the genes expression of ADPKD was compared with normal samples. Also, the gene regulatory network (GRN) based on gene- miRNA interaction was retrieved by the validated interaction from TarBase and miRTarBase databases. The NetworkAnayzer tool and MCODE plugin of Cytoscape software were used for topology and cluster analysis. Using ClueGo of Cytoscape software, Gene Ontology (GO) and functional analysis were performed.Results: Network analysis identified crucial miRNAs and genes in the network with 5407 nodes. The central nodes were determined based on degree, betweenness centrality, closeness centrality, and eccentricity and module analysis. The gene regulatory network analysis resulted in SOD2, IGF1R, MYC, GATA6, and DDX3X are critical genes and hsa-mir-4284, hsa-mir-130b-3p, hsa-mir-26b-5p, hsa-mir-335-5p have the highest centrality parameters and are known as key regulators of the network. Functional analysis was shown key paths mainly related to the regulation of cell growth and differentiation.Conclusion: The study provided high-throughput approaches to explore the main molecular mechanisms of development the vascular complications in ADPKD.

کلیدواژه ها:

ADPKD ، Aneurysm ، Microarray analysis ، Gene Regulatory Network