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TWIST1 is a direct transcriptional target of MYCN and MYC in neuroblastoma

Abdelkader Selmi1, Maud de Saint-Jean1, Anne-Catherine Jallas2

  • 1Université Lyon 1, F-69000 Lyon, France; INSERM UMR-S1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69008 Lyon, France.

Cancer Letters
|December 6, 2014
PubMed

Insights

MYCN amplification in neuroblastoma correlates with increased TWIST1 expression. Researchers confirmed TWIST1 is a direct transcriptional target of MYC proteins, impacting cancer progression.

Area of Science:

  • Molecular Oncology
  • Pediatric Cancer Research

Background:

  • MYCN amplification in neuroblastoma signifies a poor prognosis, often necessitating intensive treatment.
  • TWIST1, a transcription factor inhibiting apoptosis and differentiation, is upregulated alongside MYCN amplification.

Purpose of the Study:

  • To investigate the relationship between MYCN/MYC expression and TWIST1 upregulation in neuroblastoma.
  • To determine if MYC proteins directly regulate TWIST1 transcription.

Main Methods:

  • Analysis of clinical datasets for MYCN, MYC, and TWIST1 expression.
  • In silico promoter analysis to identify MYC regulatory motifs in the TWIST1 gene.
  • Gel shift assays and reporter activity assays to assess protein-DNA interactions and transcriptional activation.

Main Results:

  • TWIST1 is upregulated in MYCN-amplified neuroblastoma and in neuroblastoma with high MYCN or MYC expression without amplification.
  • MYC regulatory motifs (E-Boxes, INR) are present in the TWIST1 promoter.
  • N-Myc and c-Myc proteins bind to and activate the TWIST1 promoter.

Conclusions:

  • TWIST1 is a direct transcriptional target of MYC proteins in neuroblastoma.
  • This finding provides a molecular link between MYC dysregulation and TWIST1 activity in neuroblastoma pathogenesis.
Keywords:
MYCMYCNTWIST1Transcriptional regulation neuroblastoma

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