Cell Journal (Oct 2023)
Integrative Bioinformatics Analysis of The Cell Division Cycle and Ribosomal Pathways in The Rat Varicocele: Implications for Drug Discovery
Abstract
Objective: Varicocele is a common cause of male infertility, affecting a substantial proportion of infertile men. Recentstudies have employed transcriptomic analysis to identify candidate genes that may be implicated in the pathogenesisof this condition. Accordingly, this study sought to leverage rat gene expression profiling, along with protein-proteininteraction networks, to identify key regulatory genes, related pathways, and potentially effective drugs for the treatmentof varicocele.Materials and Methods: In this in-silico study, differentially expressed genes (DEGs) from the testicular tissue of 3 ratswere screened using the edgeR package in R software and the results were compared to 3 rats in the control group.Data was obtained from GSE139447. Setting a -11 and P<0.05 as cutoff points for statistical significance,up and down-regulated genes were identified. Based on Cytoscape plugins, protein-protein interaction (PPI) networkswere drawn, and hub genes were highlighted. ShinyGO was used for pathway enrichment. Finally, effective drugs wereidentified from the drug database.Results: Among the 1277 DEGs in this study, 677 genes were up-regulated while 600 genes were down-regulated in rats withvaricocele compared to the control group. Using protein-protein interaction networks, we identified the top five up-regulatedgenes and the top five down-regulated genes. Enrichment analysis showed that the up-regulated genes were associated withthe cell division cycle pathway, while the down-regulated genes were linked to the ribosome pathway. Notably, our findingssuggested that dexamethasone may be a promising therapeutic option for individuals with varicocele.Conclusion: The current investigation indicates that in varicocele the cell division cycle pathway is up-regulated whilethe ribosome pathway is down-regulated compared to controls. Based on these findings, dexamethasone could beconsidered a future candidate drug for the treatment of individuals with varicocele.
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