ArticleOncogene2012
MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- Article
- Deep Sequencing Reveals Novel Mutations inInternational journal of molecular sciences · 2025Article
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- Untangling the Role of MYC in Sarcomas and Its Potential as a Promising Therapeutic Target.International journal of molecular sciences · 2025Review
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- Mechanisms and molecular characterization of relapsed/refractory neuroblastomas.Frontiers in oncology · 2025Review
- AF1q is a universal marker of neuroblastoma that sustains N-Myc expression and drives tumorigenesis.Oncogene · 2024Article
- Synthesis and biological evaluation of dual MDM2/XIAP inhibitors based on the tetrahydroquinoline scaffold.European journal of medicinal chemistry · 2023Article
- Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment.Cancers · 2022Review
- MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.Cancers · 2022Review
- Cryptic in vitro ubiquitin ligase activity of HDMX towards p53 is probably regulated by an induced fit mechanism.Bioscience reports · 2022Article
- TP53 and TP53-associated genes are correlated with the prognosis of paediatric neuroblastoma.BMC genomic data · 2022Article
- Article
- MYCN mRNA degradation and cancer suppression by a selective small-molecule inhibitor in MYCN-amplified neuroblastoma.Frontiers in oncology · 2022Article
- From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma.Journal of personalized medicine · 2021Review
- Molecular Genetics in Neuroblastoma Prognosis.Children (Basel, Switzerland) · 2021Review
- Molecular targeting therapies for neuroblastoma: Progress and challenges.Medicinal research reviews · 2021Review
- Discovery ofJournal of medicinal chemistry · 2021Article
- Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope.Cancer letters · 2021Review
- Targeting MDM2 for Neuroblastoma Therapy: In Vitro and In Vivo Anticancer Activity and Mechanism of Action.Cancers · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The MYCN gene has a critical role in determining the clinical behavior of neuroblastoma. Although it is known that genomic amplification occurs in high-risk subsets, it remains unclear how MYCN expression is regulated in the pathogenesis of neuroblastomas. Here, we report that MYCN expression was regulated by the oncoprotein MDM2 at the post-transcriptional level and was associated with neuroblastoma cell growth. Increasing MDM2 by ectopic overexpression in the cytoplasm enhanced both mRNA and protein expression of MYCN. Mechanistic studies found that the C-terminal RING domain of the MDM2 protein bound to the MYCN mRNA's AREs within the 3'UTR and increased MYCN 3'UTR-mediated mRNA stability and translation. Conversely, MDM2 silencing by specific siRNA rendered the MYCN mRNA unstable and reduced the abundance of the MYCN protein in MYCN-amplified neuroblastoma cell lines. Importantly, this MDM2 silencing resulted in a remarkable inhibition of neuroblastoma cell growth and induction of cell death through a p53-independent pathway. Our results indicate that MDM2 has a p53-independent role in the regulation of both MYCN mRNA stabilization and its translation, suggesting that MDM2-mediated MYCN expression is one mechanism associated with growth of MYCN-associated neuroblastoma and disease progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.