Integrated Microarray to Identify the Hub miRNAs and Constructed miRNA-mRNA Network in Neuroblastoma Via Bioinformatics Analysis.

Abstract

Neuroblastomas (NB) are childhood malignant tumors originating in the sympathetic nervous system. MicroRNAs (miRNAs) play an essential regulatory role in tumorigenesis and development. In this study, NB miRNA and mRNA expression profile data in the Gene Expression Omnibus database were used to screen for differentially expressed miRNAs (DEMs) and genes (DEGs). We used the miRTarBase and miRSystem databases to predict the target genes of the DEMs, and we selected target genes that overlapped with the DEGs as candidate genes for further study. Annotations, visualization, and the DAVID database were used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the candidate genes. Additionally, the protein-protein interaction (PPI) network and miRNA-mRNA regulatory network were constructed and visualized using the STRING database and Cytoscape, and the hub modules were analyzed for function and pathway enrichment using the DAVID database and BiNGO plug-in. 107 DEMs and 1139 DEGs were identified from the miRNA and mRNA chips, respectively. 4390 overlapping target genes were identified using the two databases, and 405 candidate genes which intersected with the DEGs were selected. These candidate genes were enriched in 363 GO terms and 24 KEGG pathways. By constructing a PPI network and a miRNA-mRNA regulatory network, three hub miRNAs (hsa-miR-30e-5p, hsa-miR-15a, and hsa-miR-16) were identified. The target genes of the hub miRNAs were significantly enriched in the following pathways: microRNAs in cancer, the PI3K-Akt signaling pathway, pathways in cancer, the p53 signaling pathway, and the cell cycle. In summary, our results have identified candidate genes and pathways related to the underlying molecular mechanism of NB. These findings provide a new perspective for NB research and treatment.