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This article is part of the supplement: International Conference for Healthcare and Medical Students 2011

Open Access Oral presentation

The role of epigenetics and miRNAs in neuroblastoma development

KV Rupani1*, S Das12 and RL Stallings12

  • * Corresponding author: KV Rupani

Author Affiliations

1 Department of Cancer Genetics, Royal College of Surgeons in Ireland

2 Children's Research Center, Our Lady's Children's Hospital, Crumlin, Ireland

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BMC Proceedings 2012, 6(Suppl 4):O11  doi:10.1186/1753-6561-6-S4-O11

The electronic version of this article is the complete one and can be found online at:

Published:9 July 2012

© 2012 Rupani et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Neuroblastoma (NB) is an often fatal pediatric cancer that arises from the precursor cells of the sympathetic nervous system. 13-Cis retinoic acid is used to treat high-risk disease. A derivative, all-trans-retinoic acid (ATRA) causes genome-wide demethylation in NB cells by up-regulating miRNAs such as miR-152 and miR-26a/b which are predicted to target the methyltransferases DNMT1 and DNMT3b, respectively. The purpose of this study was to test whether ectopic over-expression of miR-26a/b, a known tumor suppressor miRNA in several other cancer types, led to reduced cell viability and DNMT3b expression in SK-N-BE NB cells. In addition, we also carried out a methylated DNA immunoprecipitation to microarrays following miR-152 over-expression in SK-N-BE cells in order to assess whether the ectopic over expression of miR-152 had any effects on genome-wide methylation.


Results showed that reduced miR-26a/b expression correlates to poor survival in patients with NB. We investigated the possibility of epigenetic factors that could control miR-26a/b expression in NB cells by treating the cells with a DNA-demethylating agent (5'-Aza-2 deoxycytodine). We did not observe any significant re-expression of miR-26a/b after application of the drug. It was further shown that ectopic over-expression of miR-26a causes a down-regulation of DNMT3b mRNA. Cell viability assays carried out following ectopic over-expression of miR-26a supported its possible involvement in reducing cell growth levels 96 hours post-transfection. Using the SHEP-TET NB cell line system, a MYCN induced repression of miR-26a/b in NB was also ruled out. Genome-wide methylation analysis following over-expression of miR-152 revealed genes that display overlapping methylation patterns as seen with ATRA treatment alone, thus allowing the identification of genes that are possibly controlled by miR-152 following suppression of DNMT1.


Having ruled out DNA methylation and MYCN as significant regulators of miR-26a/b expression during NB differentiation, we propose that other transcription factors and/or retinoic acid directly may regulate this microRNA. In addition we have identified several genes that are epigenetically regulated through the action of miR-152 and warrant further follow up to determine their importance in NB differentiation.