In silico analysis revealed the potential circRNA-miRNA-mRNA regulative network of non-small cell lung cancer (NSCLC)

Abstract

BackgroundThe primary source of death in the world is non-small cell lung cancer (NSCLC). However, NSCLCs pathophysiology is still not completely understood. The current work sought to study the differential expression of mRNAs involved in NSCLC and their interactions with miRNAs and circRNAs. MethodsWe utilized three microarray datasets (GSE21933, GSE27262, and GSE33532) from the GEO NCBI database to identify the differentially expressed genes (DEGs) in NSCLC. We employed DAVID Functional annotation tool to investigate the underlying GO biological process, molecular functions, and KEGG pathways involved in NSCLC. We performed the Protein-protein interaction (PPI) network, MCODE, and CytoHubba analysis from Cytoscape software to identify the significant DEGs in NSCLC. We utilized miRnet to anticipate and build interaction between miRNAs and mRNAs in NSCLC and ENCORI to predict the miRNA-circRNA relationships and build the ceRNA regulatory network. Finally, we executed the gene expression and Kaplan-Meier survival analysis to validate the significant DEGs in the ceRNA network utilizing TCGA NSCLC and GEPIA data. ResultsWe revealed a total of 156 overlapped DEGs (47 upregulated and 109 downregulated genes) in NSCLC. The PPI network, MCODE, and CytoHubba analysis revealed 12 hub genes (cdkn3, rrm2, ccnb1, aurka, nuf2, tyms, kif11, hmmr, ccnb2, nek2, anln, and birc5) that are associated with NSCLC. We identified that these 12 genes encode 12 mRNAs that are strongly linked with 8 miRNAs, and further, we revealed that 1 circRNA was associated with this 5 miRNA. We constructed the ceRNAs network that contained 1circRNA-5miRNAs-7mRNAs. The expression of these seven significant genes in LUAD & LUSC (NSCLC) was considerably higher in the TCGA database than in normal tissues. Kaplan-Meier survival plot reveals that increased expression of these hub genes was related to a poor survival rate in LUAD. ConclusionOverall, we developed a circRNA-miRNA-mRNA regulation network to study the probable mechanism of NSCLC.