ArticleNucleic acids research2008
p73alpha isoforms drive opposite transcriptional and post-transcriptional regulation of MYCN expression in neuroblastoma cells.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 33 citations in OpenAlex.
- Chromosome 1p36 candidate gene ZNF436 predicts the prognosis of neuroblastoma: a bioinformatic analysis.Italian journal of pediatrics · 2023Article
- Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment.Cancers · 2022Review
- Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma.Cancer medicine · 2021Article
- Review
- Silencing E3 Ubiqutin ligase ITCH as a potential therapy to enhance chemotherapy efficacy in p53 mutant neuroblastoma cells.Scientific reports · 2020Article
- ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Cell death-based treatment of neuroblastoma.Cell death & disease · 2018Review
- Expression of B-cell translocation gene 2 is associated with favorable prognosis in hepatocellular carcinoma patients and sensitizes irradiation-induced hepatocellular carcinoma cell apoptosisOncology letters · 2017Article
- Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data.Oncotarget · 2016Article
- Neuroblastoma: oncogenic mechanisms and therapeutic exploitation of necroptosis.Cell death & disease · 2015Review
- p73 regulates basal and starvation-induced liver metabolism in vivo.Oncotarget · 2015Article
- A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma.Leukemia · 2014Article
- Expression and significance of miRNA-21 and BTG2 in lung cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Apoptotic cell death in neuroblastoma.Cells · 2013Article
- BTG2 inhibits the proliferation, invasion, and apoptosis of MDA-MB-231 triple-negative breast cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- CDK4 inhibition restores G(1)-S arrest in MYCN-amplified neuroblastoma cells in the context of doxorubicin-induced DNA damage.Cell cycle (Georgetown, Tex.) · 2013Article
- Exploitation of chick embryo environments to reprogram MYCN-amplified neuroblastoma cells to a benign phenotype, lacking detectable MYCN expression.Oncogenesis · 2012Article
- Effects of BTG2 on proliferation inhibition and anti-invasion in human lung cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Article
- Article
- TNF-α response of vascular endothelial and vascular smooth muscle cells involve differential utilization of ASK1 kinase and p73.Cell death and differentiation · 2012Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MYCN activation, mainly by gene amplification, is one of the most frequent molecular events in neuroblastoma (NB) oncogenesis, and is associated with increased malignancy and decreased neuronal differentiation propensity. The frequency of concomitant loss of heterozygosity at the 1p36.3 locus, which harbours the p53 anti-oncogene homologue TP73, indicates that MYCN and p73 alterations may cooperate in the pathogenesis of NB. We have previously shown that p73 isoforms are deregulated in NB tumours and that TAp73 co-operates synergistically with p53 for apoptosis of NB cells, whereas DeltaNp73 activates the expression of neuronal differentiation genes such as BTG2. Herein, using both ectopic expression and RNA interference-mediated silencing of p73 in MYCN amplified NB cells, we show that p73alpha isoforms inhibit MYCN expression at both transcript and protein levels, in spite of transactivator effects on MYCN promoter. To explain this paradox, we found that TAp73alpha exerts negative post-transcriptional effects leading to reduced MYCN mRNA stability. RNA immunoprecipitation experiments suggest that this dominant inhibitory post-transcriptional effect could be due to an interaction between the p73 protein and MYCN mRNA, a hypothesis also raised for the regulation of certain genes by the p53 protein.
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