Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data

Chia Lang Hsu, Hsin Yi Chang, Jen Yun Chang, Wen Ming Hsu, Hsuan Cheng Huang, Hsueh Fen Juan

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

MYCN, an oncogenic transcription factor of the Myc family, is a major driver of neuroblastoma tumorigenesis. Due to the difficulty in drugging MYCN directly, revealing the molecules in MYCN regulatory networks will help to identify effective therapeutic targets for neuroblastoma therapy. Here we perform ChIP-sequencing and small RNA-sequencing of neuroblastoma cells to determine the MYCN-binding sites and MYCN-associated microRNAs, and integrate various types of genomic data to construct MYCN regulatory networks. The overall analysis indicated that MYCN-regulated genes were involved in a wide range of biological processes and could be used as signatures to identify poor-prognosis MYCN-non-amplified patients. Analysis of the MYCN binding sites showed that MYCN principally served as an activator. Using a computational approach, we identified 32 MYCN co-regulators, and some of these findings are supported by previous studies. Moreover, we investigated the interplay between MYCN transcriptional and microRNA post-transcriptional regulations and identified several microRNAs, such as miR-124-3p and miR-93-5p, which may significantly contribute to neuroblastoma pathogenesis. We also found MYCN and its regulated microRNAs acted together to repress the tumor suppressor genes. This work provides a comprehensive view of MYCN regulations for exploring therapeutic targets in neuroblastoma, as well as insights into the mechanism of neuroblastoma tumorigenesis.

Original languageEnglish
Pages (from-to)36293-36310
Number of pages18
JournalOncotarget
Volume7
Issue number24
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Fingerprint

Genomics
Neuroblastoma
MicroRNAs
Carcinogenesis
Binding Sites
RNA Sequence Analysis
Biological Phenomena
Tumor Suppressor Genes
Transcription Factors
Therapeutics
Genes

Keywords

  • Genomics
  • MicroRNA
  • MYCN
  • Neuroblastoma
  • Regulatory network

ASJC Scopus subject areas

  • Oncology

Cite this

Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data. / Hsu, Chia Lang; Chang, Hsin Yi; Chang, Jen Yun; Hsu, Wen Ming; Huang, Hsuan Cheng; Juan, Hsueh Fen.

In: Oncotarget, Vol. 7, No. 24, 01.01.2016, p. 36293-36310.

Research output: Contribution to journalArticle

Hsu, Chia Lang ; Chang, Hsin Yi ; Chang, Jen Yun ; Hsu, Wen Ming ; Huang, Hsuan Cheng ; Juan, Hsueh Fen. / Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data. In: Oncotarget. 2016 ; Vol. 7, No. 24. pp. 36293-36310.
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