ArticleCancer letters2016
MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma.
Article in Cancer letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- CAMKV kinase drives neuroblastoma growth and acts as a novel therapeutic target.The Journal of experimental medicine · 2026Article
- MYCN and helicases DDX17 and DDX5 have opposite effects on the production of readthrough-associated chimeric transcripts.Cellular and molecular life sciences : CMLS · 2026Article
- Regulation of Tau Alternative Splicing: A Novel Role for the Ribonucleoprotein RBM20.International journal of molecular sciences · 2026Article
- Targeting TRIM59 impairs RNA splicing and promotes neuroblastoma differentiation and therapeutic responses.Journal of experimental & clinical cancer research : CR · 2025Article
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- Spliceosomal vulnerability of MYCN-amplified neuroblastoma is contingent on PRMT5-mediated regulation of epitranscriptomic and metabolomic pathways.Cancer letters · 2024Article
- The Antitumour Mechanisms of Carotenoids: A Comprehensive Review.Antioxidants (Basel, Switzerland) · 2024Review
- The Regulatory Network of hnRNPs Underlying RegulatingBiomolecules · 2024Review
- Article
- CAMKV Kinase Signaling Is a Novel Therapeutic Avenue with Prognostic Relevance in Neuroblastoma.bioRxiv : the preprint server for biology · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- Inhibition of OCT4 binding at theFrontiers in oncology · 2024Article
- MYCN and SNRPD3 cooperate to maintain a balance of alternative splicing events that drives neuroblastoma progression.Oncogene · 2024Article
- Blood-based T cell receptor anti-viral CDR3s are associated with worse overall survival for neuroblastoma.Journal of cancer research and clinical oncology · 2023Article
- The RNA-binding proteins hnRNP H and F regulate splicing of a MYC-dependent HRAS exon in prostate cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN.Nature communications · 2023Article
- How Driver Oncogenes Shape and Are Shaped by Alternative Splicing Mechanisms in Tumors.Cancers · 2023Review
- Article
- Emerging roles of spliceosome in cancer and immunity.Protein & cell · 2022Review
- Alternative RNA splicing defects in pediatric cancers: new insights in tumorigenesis and potential therapeutic vulnerabilities.Annals of oncology : official journal of the European Society for Medical Oncology · 2022Review
Corrections and comments
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Authors and funding
23 authors at 9 institutions in 2 countries.
Funding
Abstract
The molecular mechanisms underlying the aggressive behavior of MYCN driven neuroblastoma (NBL) is under intense investigation; however, little is known about the impact of this family of transcription factors on the splicing program. Here we used high-throughput RNA sequencing to systematically study the expression of RNA isoforms in stage 4 MYCN-amplified NBL, an aggressive subtype of metastatic NBL. We show that MYCN-amplified NBL tumors display a distinct gene splicing pattern affecting multiple cancer hallmark functions. Six splicing factors displayed unique differential expression patterns in MYCN-amplified tumors and cell lines, and the binding motifs for some of these splicing factors are significantly enriched in differentially-spliced genes. Direct binding of MYCN to promoter regions of the splicing factors PTBP1 and HNRNPA1 detected by ChIP-seq demonstrates that MYCN controls the splicing pattern by direct regulation of the expression of these key splicing factors. Furthermore, high expression of PTBP1 and HNRNPA1 was significantly associated with poor overall survival of stage4 NBL patients (p ≤ 0.05). Knocking down PTBP1, HNRNPA1 and their downstream target PKM2, an isoform of pro-tumor-growth, result in repressed growth of NBL cells. Therefore, our study reveals a novel role of MYCN in controlling global splicing program through regulation of splicing factors in addition to its well-known role in the transcription program. These findings suggest a therapeutically potential to target the key splicing factors or gene isoforms in high-risk NBL with MYCN-amplification.
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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.