Related Experiment Video

Updated: Jan 14, 2026

Zebrafish Model of Neuroblastoma Metastasis
05:20

Zebrafish Model of Neuroblastoma Metastasis

Published on: March 14, 2021

3.2K

Distal-less homeobox 5 transactivated by MYCN contributes to progression of neuroblastoma through AKT signaling

Yi He1, Xiaosi Yu1, Chenzhao Feng2

  • 1Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cellular Signalling
|October 24, 2025
PubMed

Insights

MYCN amplification in neuroblastoma drives aggressive tumors. This study identifies DLX5 as a MYCN target gene that promotes tumor growth, metastasis, and cisplatin chemoresistance via AKT signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Neuroblastoma, a common childhood cancer, presents significant therapeutic challenges when characterized by MYCN proto-oncogene (MYCN) amplification.
  • MYCN amplification is associated with aggressive tumor behavior, invasion, and resistance to chemotherapy.

Purpose of the Study:

  • To identify downstream targets of MYCN in neuroblastoma.
  • To elucidate the role of identified targets in neuroblastoma progression and chemoresistance.
  • To investigate the underlying molecular mechanisms, including signaling pathways and transcriptional regulation.

Main Methods:

  • Differential gene expression analysis using the "limma" R package.
  • Gene silencing and overexpression experiments in neuroblastoma cell lines.
  • Correlation analysis of gene expression in clinical tissues and cell lines.
  • Cell proliferation, migration, and chemoresistance assays (cisplatin).
  • Gene set enrichment analysis, mRNA sequencing, and pathway analysis (AKT signaling).
  • Reporter assays and chromatin immunoprecipitation to confirm transcriptional regulation.

Main Results:

  • Distal-less homeobox 5 (DLX5) was identified as a direct downstream target of MYCN.
  • High DLX5 expression correlated positively with MYCN and predicted poor clinical outcomes.
  • DLX5 promoted neuroblastoma proliferation, migration, and cisplatin chemoresistance.
  • Enriched pathways in DLX5 high-expression samples included base and nucleotide excision repair.
  • AKT signaling pathway activation was identified as a key mechanism mediating DLX5's effects.
  • MYCN directly binds to the DLX5 promoter, activating its transcription.

Conclusions:

  • MYCN transcriptionally activates DLX5, which promotes neuroblastoma growth, metastasis, and chemoresistance.
  • The MYCN-DLX5-AKT axis represents a potential therapeutic target for neuroblastoma.
  • This study provides novel insights into the molecular mechanisms driving neuroblastoma progression and treatment resistance.
Keywords:
AKT signalingDistal-less homeobox 5MYCN proto-oncogeneNeuroblastomaPediatric tumor

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