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Oncol Rep. 2017 Jul;38(1):3-20. doi: 10.3892/or.2017.5701. Epub 2017 Jun 6.

A sketch of known and novel MYCN-associated miRNA networks in neuroblastoma.

Author information

1
Department of Paediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, I-00161 Rome, Italy.
2
Genomnia s.r.l., I-20091 Bresso, MI, Italy.
3
Department of Molecular Medicine, Sapienza University of Rome, I-00161 Rome, Italy.
4
Department of Paediatric Surgery, Alder Hey Children's NHS Foundation Trust, L12 2AP Liverpool, UK.
5
Department of Oncology, Alder Hey Children's NHS Foundation Trust, L12 2AP Liverpool, UK.
6
Department of Perinatal and Paediatric Pathology, Alder Hey Children's NHS Foundation Trust, L12 2AP Liverpool, UK.
7
Department of Experimental Medicine, Sapienza University of Rome, I-00161 Rome, Italy.

Abstract

Neuroblastoma (NB) originates from neural crest-derived precursors and represents the most common childhood extracranial solid tumour. MicroRNAs (miRNAs), a class of small non-coding RNAs that participate in a wide variety of biological processes by regulating gene expression, appear to play an essential role within the NB context. High-throughput next generation sequencing (NGS) was applied to study the miRNA transcriptome in a cohort of NB tumours with and without MYCN-amplification (MNA and MNnA, respectively) and in dorsal root ganglia (DRG), as a control. Out of the 128 miRNAs differentially expressed in the NB vs. DRG comparison, 47 were expressed at higher levels, while 81 were expressed at lower levels in the NB tumours. We also found that 23 miRNAs were differentially expressed in NB with or without MYCN-amplification, with 17 miRNAs being upregulated and 6 being downregulated in the MNA subtypes. Functional annotation analysis of the target genes of these differentially expressed miRNAs demonstrated that many mRNAs were involved in cancer-related pathways, such as DNA-repair and apoptosis as well as FGFR and EGFR signalling. In particular, we found that miR-628-3p negatively affects MYCN gene expression. Furthermore, we identified a novel miRNA candidate with variable expression in MNA vs. MNnA tumours, whose putative target genes are implicated in the mTOR pathway. The present study provides further insight into the molecular mechanisms that correlate miRNA dysregulation to NB development and progression.

PMID:
28586032
PMCID:
PMC5492854
DOI:
10.3892/or.2017.5701
[Indexed for MEDLINE]
Free PMC Article

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