In Silico Integrative Approach Revealed Key MicroRNAs and AssociatedTarget Genes in Cardiorenal Syndrome

摘要

Cardiorenal syndromes constellate primary dysfunction of either heart or kidneywhereby one organ dysfunction leads to the dysfunction of another. The role ofseveral microRNAs (miRNAs) has been implicated in number of diseases, includinghypertension, heart failure, and kidney diseases. Wide range of miRNAs has beenidentified as ideal candidate biomarkers due to their stable expression. Currentstudy was aimed to identify crucial miRNAs and their target genes associatedwith cardiorenal syndrome and to explore their interaction analysis. Threedifferentially expressed microRNAs (DEMs), namely, hsa-miR-4476, hsa-miR-345-3p,and hsa-miR-371a-5p, were obtained from {"type":"entrez-geo","attrs":{"text":"GSE89699","term_id":"89699"}}GSE89699 and {"type":"entrez-geo","attrs":{"text":"GSE87885","term_id":"87885"}}GSE87885 microRNA datasets, using R/GEO2R tools. Furthermore, literature mining resulted in theretrieval of 15 miRNAs from scientific research and review articles. ThemiRNAs-gene networks were constructed using miRNet (a Web platform ofmiRNA-centric network visual analytics). CytoHubba (Cytoscape plugin) wasadopted to identify the modules and the top-ranked nodes in the network based onDegree centrality, Closeness centrality, Betweenness centrality, and Stresscentrality. The overlapped miRNAs were further used in pathway enrichmentanalysis. We found that hsa-miR-21-5p was common in 8 pathways out of the top10. Based on the degree, 5 miRNAs, namely, hsa-mir-122-5p, hsa-mir-222-3p,hsa-mir-21-5p, hsa-mir-146a-5p, and hsa-mir-29b-3p, are considered as keyinfluencing nodes in a network. We suggest that the identified miRNAs and theirtarget genes may have pathological relevance in cardiorenal syndrome (CRS) andmay emerge as potential diagnostic biomarkers.