A microRNA and mRNA signature of neuroblastoma LAN-5 cells expressing MBP-1

An alternative translated product of the ENO1 gene, known as MBP-1 (c-Myc-promoter Binding Protein-1), acts as a negative regulator of the c-MYC oncogene, ERBB2 and COX-2 genes. The ENO1 gene is located in chromosomal region 1p36.2, within the common region of deletion detected in Neuroblastoma (NB) often associated with the amplification of MYCN gene. We have previously shown that MBP-1 interacts with MYCN gene promoter and negatively regulates its expression acting as an oncosuppressor protein in LAN-5 cells. Furthermore, in NB cells MBP-1 overexpression significantly reduces migration and proliferation and ultimately induces cell death. To investigate the functional role of MBP-1 in NB, we performed global gene and miRNA expression analyses, using microarray technology, to identify genes and miRNAs that are differentially expressed (DE) in LAN-5 cells in the absence or in the presence of MBP-1 expression. The analysis of the gene expression profiles confirmed that MBP-1 expression results in MYCN downregulation and p21cip, BAX and ?-enolase overexpression and allowed us to identify other MBP-1 putative targets. The miRNA expression analysis resulted in the identification of several miRNAs with tumor-suppressor activity. In addition, a comparison of the pathway enrichment analyses obtained from MBP-1 DE genes and MBP-1 DE miRNA targets provided information on the biological functions of these genes and highlighted novel interesting regulative networks. In general, the expression profiles analyses confirmed that MBP-1 plays an important role in cell growth, the activation of apoptosis and in the migration potential of NB LAN-5 cells, making it a good candidate as a therapeutic target for neuroblastoma.