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

研究成果: 雜誌貢獻文章

16 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)36293-36310
頁數18
期刊Oncotarget
7
發行號24
DOIs
出版狀態已發佈 - 一月 1 2016
對外發佈Yes

ASJC Scopus subject areas

  • Oncology

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