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

In neuroblastoma, MYCN amplification is associated with a worse prognosis and is a criterion used in the clinic to provide intensive treatments to children even with localized disease. In correlation with MYCN amplification, upregulation of TWIST), a transcription factor playing a crucial role in inhibition of apoptosis and differentiation, was previously reported. Clinical data set analysis of MYCN, MYC and TWIST1 expression permits us to confirm that TWIST) expression is upregulated in MYCN amplified neuroblastoma but also in a subset of neuroblastoma harboring high expression of MYCN or MYC without gene amplification. In silica analyses reveal the presence of several MYC regulatory motifs (E-Boxes and INR) within the TWIST) promoter. Using gel shift assay and reporter activity assays, we demonstrate that both N-Myc and c-Myc proteins can bind and activate the TWIST) promoter. Therefore, we propose TWIST) as a direct MYC transcriptional target. (C) 2014 Elsevier Ireland Ltd. All rights reserved.