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

Abstract

Cardiorenal syndromes constellate primary dysfunction of either heart or kidney whereby one organ dysfunction leads to the dysfunction of another. The role of several microRNAs (miRNAs) has been implicated in number of diseases, including hypertension, heart failure, and kidney diseases. Wide range of miRNAs has been identified as ideal candidate biomarkers due to their stable expression. Current study was aimed to identify crucial miRNAs and their target genes associated with cardiorenal syndrome and to explore their interaction analysis. Three differentially expressed microRNAs (DEMs), namely, hsa-miR-4476, hsa-miR-345-3p, and hsa-miR-371a-5p, were obtained from GSE89699 and GSE87885 microRNA data sets, using R/GEO2R tools. Furthermore, literature mining resulted in the retrieval of 15 miRNAs from scientific research and review articles. The miRNAs-gene networks were constructed using miRNet (a Web platform of miRNA-centric network visual analytics). CytoHubba (Cytoscape plugin) was adopted to identify the modules and the top-ranked nodes in the network based on Degree centrality, Closeness centrality, Betweenness centrality, and Stress centrality. The overlapped miRNAs were further used in pathway enrichment analysis. We found that hsa-miR-21-5p was common in 8 pathways out of the top 10. 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 key influencing nodes in a network. We suggest that the identified miRNAs and their target genes may have pathological relevance in cardiorenal syndrome (CRS) and may emerge as potential diagnostic biomarkers.

Identification of the Key miRNAs and Genes Associated with the Regulation of Non-Small Cell Lung Cancer: A Network-Based Approach

“…Therefore, these signature genes/miRNAs can largely offer benefits as biomarkers to other cancers as well, besides NSCLC, in diagnosis. Similar reports have also demonstrated the significance of key miRNAs and associated target genes in various syndromes [115][116][117]. It is noteworthy to mention that SAMD8 is exclusive to our study like miR-572.…”

New Insight in Cardiorenal Syndrome: From Biomarkers to Therapy

“…An increasing body of evidence supports the role of micro RNAs (miRNAs) in pathophysiological conditions of heart and kidney. miRNAs are involved in different biological processes, including cellular differentiation and proliferation, apoptosis, inflammation, hemostasis, myocardial fibrosis, myocyte hypertrophy, cardiac remodeling and regeneration [ 63 , 64 ]. It has been shown that high levels of MiR-21 may be associated with cardiac remodeling and fibrosis of both the heart and kidneys [ 65 , 66 ] by several mechanisms, including the activation of collagen and alpha-smooth muscle actin (a-SMA) protein expression in myofibroblasts in the heart, as well as the inhibition of Notch2 expression in the kidney [ 67 ].…”

Progress and Challenges of Understanding Cardiorenal Syndrome Type 3

“…In addition the participation in pathophysiology, miRNAs are also emerging biomarkers in the context of CRS. Ahmed et al [135] carried out an in silico research of miRNAs in the CRS, in which hsa-miR-21-5p was found in 8 pathways out of principal 10, and more 5 miRNAs were prominent, hsa-miR-122-5p, hsa-miR-222-3p, hsa-miR-146a-5p, and hsa-miR-29b-3p. The research suggests that the found 6 miR-NAs may be promising diagnostic biomarkers.…”