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Extension of microRNA expression pattern associated with high-risk neuroblastoma

  • Research Article
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Tumor Biology

Abstract

Clinical behavior of neuroblastoma (NBL) is remarkably heterogeneous, as it ranges from spontaneous regression to aggressive clinical phenotype and death. There is increasing body of evidence demonstrating that microRNAs could be considered the potential biomarkers for clinical applications in NBL. In this report, we focus on molecular characterization of high-risk as well as low-risk and intermediate-risk NBL cases in the context of the microRNA expression profile that is specific for the given risk category of the disease. We investigated a total of 30 NBL patients, out of whom there were 19 patients with low- to intermediate-risk and 11 with high-risk NBLs as defined by the Clinical Oncology Group. We determined the expression profiles of 754 microRNAs (miRNAs), whereas the miRNA expression levels were normalized to RNU44, mean expression levels were calculated, and data were analyzed by use of the microarray biostatistical approaches. We identified the signature of 38 miRNAs differentially expressed between these groups of NBL patients (P < 0.05): 17 miRNAs were upregulated and 21 miRNAs were downregulated in the tumors of high-risk NBL patients. We confirm some of the previous observations and we report several new microRNAs associated with aggressive NBL, both being relevant subjects for further translational validation and functional studies.

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Abbreviations

Bcl2:

B cell lymphoma

COG:

Children’s Oncology Group

HR:

High risk

IMR:

Intermediate risk

INPC:

International Neuroblastoma Pathology Classification

INSS:

International Neuroblastoma Staging System

miRNA:

microRNA

MYCN:

V-myc myelocytomatosis viral-related oncogene, neuroblastoma-derived (avian)

NBL:

Neuroblastoma

NEUROD1:

Neurogenic differentiation 1

LR:

Low risk

TLDA:

TaqMan low-density arrays

TrkA/TrkB:

Tyrosin-related kinase A/tyrosine-related kinase B

References

  1. Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 2003;3(3):203–16.

    Article  PubMed  CAS  Google Scholar 

  2. Park JR, Eggert A, Caron H. Neuroblastoma: biology, prognosis, and treatment. Pediatr Clin North Am. 2008;55(1):97–120.

    Article  PubMed  Google Scholar 

  3. Speleman F, De Preter K, Vandesompele J. Neuroblastoma genetics and phenotype: a tale of heterogeneity. Semin Cancer Biol. 2011;21(4):238–44.

    Article  PubMed  CAS  Google Scholar 

  4. Iorio MV, Croce CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 2012;4(3):143–59.

    Article  PubMed  CAS  Google Scholar 

  5. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14.

    Article  PubMed  CAS  Google Scholar 

  6. Chen Y, Stallings RL. Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 2007;67(3):976–83.

    Article  PubMed  CAS  Google Scholar 

  7. Bray I, Bryan K, Prenter S, Buckley PG, Foley NH, Murphy DM, et al. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival. PLoS One. 2009;4(11):e7850.

    Article  PubMed  Google Scholar 

  8. Schulte JH, Schowe B, Mestdagh P, Kaderali L, Kalaghatgi P, Schlierf S, et al. Accurate prediction of neuroblastoma outcome based on miRNA expression profiles. Int J Cancer. 2010;127(10):2374–85.

    Article  PubMed  CAS  Google Scholar 

  9. Buckley PG, Alcock L, Bryan K, Bray I, Schulte JH, Schramm A, et al. Chromosomal and microRNA expression patterns reveal biologically distinct subgroups of 11q- neuroblastoma. Clin Cancer Res. 2010;16(11):2971–8.

    Article  PubMed  CAS  Google Scholar 

  10. Guo J, Dong Q, Fang Z, Chen X, Lu H, Wang K, et al. Identification of miRNAs that are associated with tumor metastasis in neuroblastoma. Cancer Biol Ther. 2010;9(6):446–52.

    Article  PubMed  CAS  Google Scholar 

  11. Schulte JH, Marschall T, Martin M, Rosenstiel P, Mestdagh P, Schlierf S, et al. Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma. Nucleic Acids Res. 2010;38(17):5919–28.

    Article  PubMed  CAS  Google Scholar 

  12. Gattolliat CH, Thomas L, Ciafre SA, Meurice G, Le Teuff G, Job B, et al. Expression of miR-487b and miR-410 encoded by 14q32.31 locus is a prognostic marker in neuroblastoma. Br J Cancer. 2011;105(9):1352–61.

    Article  PubMed  CAS  Google Scholar 

  13. Lin RJ, Lin YC, Chen J, Kuo HH, Chen YY, Diccianni MB, et al. microRNA signature and expression of Dicer and Drosha can predict prognosis and delineate risk groups in neuroblastoma. Cancer Res. 2010;70(20):7841–50.

    Article  PubMed  CAS  Google Scholar 

  14. De Preter K, Mestdagh P, Vermeulen J, Zeka F, Naranjo A, Bray I, et al. miRNA expression profiling enables risk stratification in archived and fresh neuroblastoma tumor samples. Clin Cancer Res. 2011;17(24):7684–92.

    Article  PubMed  Google Scholar 

  15. De Brouwer S, Mestdagh P, Lambertz I, Pattyn F, De Paepe A, Westermann F, et al. Dickkopf-3 is regulated by the MYCN-induced miR-17-92 cluster in neuroblastoma. Int J Cancer. 2011;130(11):2591–8.

    Article  PubMed  Google Scholar 

  16. Tivnan A, Tracey L, Buckley PG, Alcock LC, Davidoff AM, Stallings RL. MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. BMC Cancer. 2011;11:33.

    Article  PubMed  CAS  Google Scholar 

  17. Zheng H, Zeng Y, Zhang X, Chu J, Loh HH, Law PY. mu-Opioid receptor agonists differentially regulate the expression of miR-190 and NeuroD. Mol Pharmacol. 2009;77(1):102–9.

    Article  PubMed  Google Scholar 

  18. Liu Y, Encinas M, Comella JX, Aldea M, Gallego C. Basic helix-loop-helix proteins bind to TrkB and p21(Cip1) promoters linking differentiation and cell cycle arrest in neuroblastoma cells. Mol Cell Biol. 2004;24(7):2662–72.

    Article  PubMed  CAS  Google Scholar 

  19. Ryan J, Tivnan A, Fay J, Bryan K, Meehan M, Creevey L, et al. MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer. 2012;107(6):967–76. doi:10.1038/bjc.2012.356.

    Article  PubMed  CAS  Google Scholar 

  20. Yang Z, Ren F, Liu C, He S, Sun G, Gao Q, et al. dbDEMC: a database of differentially expressed miRNAs in human cancers. BMC Genomics. 2010;11 Suppl 4:S5.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was funded by the Childhood Cancer Foundation—Krtek, by the Institutional Resources for Supporting the Research Organization provided by the Ministry of Health of the Czech Republic in 2012, and by the project “CEITEC—Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068) and “RECAMO—Regional Centre for Applied Molecular Oncology” (CZ.1.05/2.1.00/03.0101).

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Correspondence to Julie Bienertova-Vasku.

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Bienertova-Vasku, J., Mazanek, P., Hezova, R. et al. Extension of microRNA expression pattern associated with high-risk neuroblastoma. Tumor Biol. 34, 2315–2319 (2013). https://doi.org/10.1007/s13277-013-0777-0

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  • DOI: https://doi.org/10.1007/s13277-013-0777-0

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