Screening of core genes and prediction of ceRNA regulation mechanism of circRNAs in nasopharyngeal carcinoma by bioinformatics analysis.

Abstract

Background: Nasopharyngeal carcinoma (NPC) represents a highly aggressive malignant tumor. Competing endogenous RNAs (ceRNA) regulation is a common regulatory mechanism in tumors. The ceRNA network links the functions between mRNAs and ncRNAs, thus playing an important regulatory role in diseases. This study screened the potential key genes in NPC and predicted regulatory mechanisms using bioinformatics analysis. Methods: The merged microarray data of three NPC-related mRNA expression microarrays from the Gene Expression Omnibus (GEO) database and the expression data of tumor samples or normal samples from the nasopharynx and tonsil in The Cancer Genome Atlas (TCGA) database were both subjected to differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA). The results from two different databases were intersected with WGCNA results to obtain potential regulatory genes in NPC, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. The hub-gene in candidate genes was discerned through Protein-Protein Interaction (PPI) analysis and its upstream regulatory mechanism was predicted by miRwalk and circbank databases. Results: Totally 68 upregulated genes and 96 downregulated genes in NPC were screened through GEO and TCGA. According to WGCNA, the NPC-related modules were screened from GEO and TCGA analysis results, and the genes in the modules were obtained. After the results of differential analysis and WGCNA were intersected, 74 differentially expressed candidate genes associated with NPC were discerned. Finally, fibronectin 1 (FN1) was identified as a hub-gene in NPC. Prediction of upstream regulatory mechanisms of FN1 suggested that FN1 may be regulated by ceRNA mechanisms involving multiple circRNAs, thereby influencing NPC progression through ceRNA regulation. Conclusion: FN1 is identified as a key regulator in NPC development and is likely to be regulated by numerous circRNA-mediated ceRNA mechanisms.