Construction of miRNA-mRNA network for the identification of key biological markers and their associated pathways in IgA nephropathy by employing the integrated bioinformatics analysis

Abstract

Background About half-century ago, Immunoglobulin A nephropathy (IgAN) was discovered as a complicated disease with frequent clinical symptoms. Until now, exact mechanism underlying the pathogenesis of IgAN is poorly known. Therefore, current study was aimed to understand the molecular mechanism of IgAN by identifying the key miRNAs and their targeted hub genes. The key miRNAs might contribute to the diagnosis and therapy of IgAN, and could turn out to be a new star in the field of IgAN. Methods The microarray datasets were downloaded from Gene Expresssion Omnibus (GEO) database and analyzed using R package (LIMMA) in order to obtain differential expressed genes (DEGs). Then, the hub genes were identified using cytoHubba plugin of cytoscpae tool and other bioinformatics approaches including protein-protein interaction (PPI) network analysis, module analysis, and miRNA-hub gene network construction was also performed. Results A total of 348 DEGs were identified, of which 107 were upregulated genes and 241 were downregulated genes. Subsequently, the 12 overlapped genes were predicted from cytoHubba, and considered as hub genes. Moreover, a network among miRNA-hub genes was created to explore the correlation between the hub genes and their targeted miRNAs. Network construction ultimately lead to the identification of nine gene named FN1, EGR1, FOS, JUN, SERPINE1, MMP2, ATF3, MYC, and IL1B and one novel key miRNA namely, has-miR-144-3p as biomarker for diagnosis and therapy of IgAN. Conclusion This study updates the information and yield a new perspective in context of understanding the pathogenesis and development of IgAN. In future, key miRNAs might be capable of improving the personalized detection and therapies for IgAN. In vivo and in vitro investigation of miRNAs and pathway interaction is essential to delineate the specific roles of the novel miRNAs, which may help to further reveal the mechanisms underlying IgAN.

Identification of key candidate genes for IgA nephropathy using machine learning and statistics based bioinformatics models

“…According to the GO analysis for BP, the DEGs were statistically significantly associated with inflammatory, camp, and cellular responses to lipopolysaccharide, cytokine-mediated signaling pathway, and neutrophil chemotaxis. Among them, some previous studies found response to inflammatory 10 , 21 , 30 , response to camp 10 , 21 , 22 , 31 , and cellular response to lipopolysaccharide 10 , 21 as highly significant GO terms.…”

Network Pharmacology Approach for Medicinal Plants: Review and Assessment

“…The advent of highly efficient technologies for analyzing big data has opened new avenues for discovering more intriguing and effective diagnostic and therapeutic solutions [ 5 , 21 ]. Understanding how well the proteins interfere with the functioning of the complex regulatory machinery is critical [ 22 ].…”

“…However, there is an urgent need to develop innovative approaches to target the entire biological networks that underlie the disease [ 3 , 4 ]. Thus, understanding the molecular pathways that govern disease prognosis are critical in the fight against complicated diseases [ 5 ].…”

Network Pharmacology and Bioinformatics Approach Reveals the Multi-Target Pharmacological Mechanism of Fumaria indica in the Treatment of Liver Cancer

“…Rather than focusing on the single-target procedure in which drugs work, it looks at the multi-target process in which drugs work [10]. Hence, the new drug development process and strategy combines computer science, molecular biology, and pharmacology [11][12][13][14][15]. A systematic and comprehensive exposition of 'disease-target protein-drug' linkages may be constructed utilizing professional networks and existing resources such as genes, proteins, illnesses, and medications [16].…”