Regulatory Network Analysis of MicroRNAs and Genes in Neuroblastoma

Abstract

Neuroblastoma (NB), the most common extracranial solid tumor, accounts for 10% of childhood cancer.To date, scientists have gained quite a lot of knowledge about microRNAs (miRNAs) and their genes in NB.Discovering inner regulation networks, however, still presents problems. Our study was focused on determiningdifferentially-expressed miRNAs, their target genes and transcription factors (TFs) which exert profound influenceon the pathogenesis of NB. Here we constructed three regulatory networks: differentially-expressed, relatedand global. We compared and analyzed the differences between the three networks to distinguish key pathwaysand significant nodes. Certain pathways demonstrated specific features. The differentially-expressed networkconsists of already identified differentially-expressed genes, miRNAs and their host genes. With this network, wecan clearly see how pathways of differentially expressed genes, differentially expressed miRNAs and TFs affecton the progression of NB. MYCN, for example, which is a mutated gene of NB, is targeted by hsa-miR-29a andhsa-miR-34a, and regulates another eight differentially-expressed miRNAs that target genes VEGFA, BCL2,REL2 and so on. Further related genes and miRNAs were obtained to construct the related network and it wasobserved that a miRNA and its target gene exhibit special features. Hsa-miR-34a, for example, targets geneMYC, which regulates hsa-miR-34a in turn. This forms a self-adaption association. TFs like MYC and PTENhaving six types of adjacent nodes and other classes of TFs investigated really can help to demonstrate that TFsaffect pathways through expressions of significant miRNAs involved in the pathogenesis of NB. The presentstudy providing comprehensive data partially reveals the mechanism of NB and should facilitate future studiesto gain more significant and related data results for NB.