Regulatory network analysis of microRNAs and genes in neuroblastoma.

Li Wang,Ning Wang,Ming-Hui Zhu,Xiang-Jiu Che,Jie Li

doi:10.7314/apjcp.2014.15.18.7645

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 determining differentially-expressed miRNAs, their target genes and transcription factors (TFs) which exert profound influence on the pathogenesis of NB. Here we constructed three regulatory networks: differentially-expressed, related and global. We compared and analyzed the differences between the three networks to distinguish key pathways and significant nodes. Certain pathways demonstrated specific features. The differentially-expressed network consists of already identified differentially-expressed genes, miRNAs and their host genes. With this network, we can clearly see how pathways of differentially expressed genes, differentially expressed miRNAs and TFs affect on the progression of NB. MYCN, for example, which is a mutated gene of NB, is targeted by hsa-miR-29a and hsa-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 was observed that a miRNA and its target gene exhibit special features. Hsa-miR-34a, for example, targets gene MYC, which regulates hsa-miR-34a in turn. This forms a self-adaption association. TFs like MYC and PTEN having six types of adjacent nodes and other classes of TFs investigated really can help to demonstrate that TFs affect pathways through expressions of significant miRNAs involved in the pathogenesis of NB. The present study providing comprehensive data partially reveals the mechanism of NB and should facilitate future studies to gain more significant and related data results for NB.

Highlights

Neuroblastoma (NB) is the fourth most common malignancy of childhood
There are three transcription factors (TFs), i.e., MYCN, PDGFA, TP73, and another 11 differentially expressed genes such as BCL2 and VEGFA, and 37 differentially expressed miRNAs and their host genes in this network, which are regarded as essential regulatory elements
We see the connection between MYCN and VEGFA, BCL2, and understand that gene MYCN can affect on the expression of gene VEGFA and BCL2 by regulating hsa-miR-17 in order to regulate cellular processes, such as proliferation, cell growth and protein synthesis

Summary

Introduction

Neuroblastoma (NB) is the fourth most common malignancy of childhood. And it is the most common intraabdominal malignancy of infancy and the most common extracranial solid tumor of childhood.Transcription factors (TFs) are one kind of proteins, which can bind to specific DNA sequences to control the transcription of genetic information from DNA to messenger RNA (Karin, 1990; Latchman, 1997). Neuroblastoma (NB) is the fourth most common malignancy of childhood. It is the most common intraabdominal malignancy of infancy and the most common extracranial solid tumor of childhood. Transcription factors (TFs) are one kind of proteins, which can bind to specific DNA sequences to control the transcription of genetic information from DNA to messenger RNA (Karin, 1990; Latchman, 1997) They have the ability to regulate gene expression at the transcription level alone or with other proteins. MicroRNAs (miRNAs) are small (about 22 nucleotides) non-coding RNAs, which are involved in various biological processes including cell proliferation, differentiation and apoptosis They can regulate the expressions of genes at the posttranscriptional level and become important cellular components (Chen et al, 2007)

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