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Positive auto-regulation of MYCN in human neuroblastoma
- Source :
- Biochemical and Biophysical Research Communications. 390:21-26
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- MYCN oncogene is one of the most important regulators affecting the prognosis of neuroblastoma and is frequently amplified in the high-risk subsets. Despite its clinical significance, it remains unclear how the MYCN expression is regulated in human neuroblastomas. Here, we found the presence of a positive auto-regulatory mechanism of MYCN. Enforced expression of MYCN induced endogenous MYCN mRNA expression in SK-N-AS neuroblastoma cells with a single copy of MYCN gene. Luciferase reporter assay revealed that MYCN protein activates its own promoter activity in a dose-dependent manner and the downstream region relative to the transcription start sites is responsible for the activation. Furthermore, ChIP analysis showed that MYCN is directly recruited onto the intron 1 region of MYCN gene which contains two putative E-box sites. Intriguingly, in response to all-trans-retinoic acid (ATRA), MYCN was down-regulated in MYCN-amplified SK-N-BE neuroblastoma cells, and the recruitment of MYCN protein onto its own intron 1 region was reduced in association with an induction of neuronal differentiation. Collectively, our present results suggest that MYCN contributes to its own expression by forming a positive auto-regulatory loop in neuroblastoma cells.
- Subjects :
- Chromatin Immunoprecipitation
Neurogenesis
Biophysics
Tretinoin
Biology
Biochemistry
N-Myc Proto-Oncogene Protein
E-Box Elements
Neuroblastoma
Cell Line, Tumor
medicine
Homeostasis
Humans
RNA, Messenger
Nuclear protein
Promoter Regions, Genetic
neoplasms
Molecular Biology
Gene
Neurons
Oncogene Proteins
Regulation of gene expression
Genome, Human
Intron
Nuclear Proteins
Cell Biology
medicine.disease
Molecular biology
Gene Expression Regulation
N-Myc
Chromatin immunoprecipitation
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 390
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....25e39ea9ca37dbf7fddb76371d9a5c3a