TY - JOUR
T1 - TWIST1 is a direct transcriptional target of MYCN and MYC in neuroblastoma
AU - Selmi, Abdelkader
AU - de Saint-Jean, Maud
AU - Jallas, Anne Catherine
AU - Garin, Elisabeth
AU - Hogarty, Michael D.
AU - Bénard, Jean
AU - Puisieux, Alain
AU - Marabelle, Aurélien
AU - Valsesia-Wittmann, Sandrine
N1 - Publisher Copyright:
© 2014 Elsevier Ireland Ltd.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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 TWIST1, 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 TWIST1 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 silico analyses reveal the presence of several MYC regulatory motifs (E-Boxes and INR) within the TWIST1 promoter. Using gel shift assay and reporter activity assays, we demonstrate that both N-Myc and c-Myc proteins can bind and activate the TWIST1 promoter. Therefore, we propose TWIST1 as a direct MYC transcriptional target.
AB - 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 TWIST1, 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 TWIST1 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 silico analyses reveal the presence of several MYC regulatory motifs (E-Boxes and INR) within the TWIST1 promoter. Using gel shift assay and reporter activity assays, we demonstrate that both N-Myc and c-Myc proteins can bind and activate the TWIST1 promoter. Therefore, we propose TWIST1 as a direct MYC transcriptional target.
KW - MYC
KW - MYCN
KW - TWIST1
KW - Transcriptional regulation neuroblastoma
UR - http://www.scopus.com/inward/record.url?scp=84920576922&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2014.11.056
DO - 10.1016/j.canlet.2014.11.056
M3 - Article
C2 - 25475555
AN - SCOPUS:84920576922
SN - 0304-3835
VL - 357
SP - 412
EP - 418
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -