Comprehensive Analysis of Key Genes Associated with ceRNA Networks in Nasopharyngeal Carcinoma Based on Bioinformatics Analysis

Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that has high morbidity rates in the east and southeast Asia, especially in South China. However, the molecular mechanisms of NPC remain largely unknown. Therefore, it is urgent to explore the pathogenesis of NPC and search for the potential biomarkers and the prognostic indicators for NPC precision treatment. We comprehensively analyzed the mRNAs, long non-coding RNAs (lncRNAs), and microRNA (miRNAs) from the full transcriptome sequencing data of our hospital (5 normal vs. 5 NPC tissues) and from six microarray datasets (62 normal vs. 334 NPC tissues) downloaded from the Gene Expression Omnibus (GEO) dataset (GSE12452, GSE13597, GSE95166, GSE126683, GSE70970, GSE43039) to see gene expression clustering by using principal components analysis (PCA). Differentially expressed genes (DEGs) were identified using the Limma package of the R software and visualized through volcano plot and Venn diagram. The gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and gene set enrichment analysis (GSEA) were performed for annotation, visualization, and integrated discovery. Furthermore, we constructed mRNA-miRNA-lncRNA (ceRNA) networks using miRanda and TargetScan and obtained the protein-protein interaction (PPI) network of DEGs via STRING database. The hub genes were identified by MCODE, NetworkAnalyzer and CytoHubba plugin. In total, 61 mRNAs, 14miRNAs and 10 lncRNAs were discovered to be DEGs after the intersection of three mRNAs datasets, two miRNAs datasets and three lncRNAs datasets. Based on the GO analysis, which includes annotation of biological processes (BPs), molecular functions (MFs) and cellular components (CCs), we found that changes in NPC were mainly enriched in the chromosomal region, sister chromatid segregation, nuclear chromosome segregation, and DNA replication. The KEGG pathway enrichment analysis indicated that the DEGs were mainly concentrated in DNA replication and cell cycle. Moreover, the GSEA suggested that the MAPK signaling pathway, PI3K-AKT signaling pathway, and apoptotic pathway were largely involved in the initiation and development of NPC. Finally, using the PPI network, a total of 20 hub genes (NUSAP1, RACGAP1, PRC1, KIF4A, TOP2A, PBK, KIF2C, TPX2, CENPU, OIP5, TTK, MAD2L1, NDC80, BIRC5, MELK, CENPF, FOXM1, TYMS, CDK1 and CEP55) were uncovered. Our findings may provide additional insights into the biological characteristics of NPC via integrative analysis of the microarray datasets and the total transcriptome sequencing, offering potential therapeutic targets, biomarkers and prognostic indicators for NPC.