ArticleThe Journal of clinical investigation2016
Antisense oligonucleotide-mediated MDM4 exon 6 skipping impairs tumor growth.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
128 citing papers in PubMed, 165 citations in OpenAlex.
- Targeting SUV39H2 exon skipping reverses resistance to CDK4/6 inhibitors via transcriptional activation of p21.Science advances · 2026Article
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- TIA1 depletion enhances CLSTN1 exon 11 inclusion to facilitate Epithelial-to-Mesenchymal transition and breast cancer metastasis.Oncogene · 2026Article
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Global landscape of protein-coding and long non-coding RNA alternative splicing and regulation in the human esophageal squamous cell carcinoma.Cancer cell international · 2026Article
- Nucleic Acid Therapeutics for "Undruggable" Cancer Targets: Mechanisms, Challenges, and Prospects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Pharmacological targeting of SF3a1-MDM4 splicing vulnerability in ovarian cancer with rifaximin and antisense oligonucleotide.Journal of translational medicine · 2026Article
- A synergistic interaction between PRMT5 and LSD1 inhibitors in AML.Science advances · 2026Article
- Antisense oligonucleotide targeting TARDBP-EGFR splicing axis inhibits progression of oral squamous cell carcinoma through ABCA1-regulated cholesterol efflux.International journal of oral science · 2026Article
- Splicing factor FUS facilitates the progression of PIT1-lineage PitNETs by upregulating MDM2.Theranostics · 2026Article
- Nonsense-mediated mRNA decay: a key regulatory system engaged in cancer.Cell communication and signaling : CCS · 2025Review
- SF3A3 Drives Tumorigenesis in Endometrial Cancer by Enhancing c-FOS Expression and Represents a Potential Therapeutic Target.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SRSF3 undergoes phase separation in lung cancer and is associated with immunity and ferroptosis.Scientific reports · 2025Article
- Transcriptome-wide decoding the roles of aberrant splicing in melanoma MAPK-targeted resistance evolution.EMBO reports · 2025Article
- Ribosomal RNA transcription regulates splicing through ribosomal protein RPL22.Cell chemical biology · 2025Article
- MitoTracer facilitates the identification of informative mitochondrial mutations for precise lineage reconstruction.PLoS computational biology · 2025Article
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Alternative Splicing: Emerging Roles in Anti-Aging Strategies.Biomolecules · 2025Review
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MDM4 is a promising target for cancer therapy, as it is undetectable in most normal adult tissues but often upregulated in cancer cells to dampen p53 tumor-suppressor function. The mechanisms that underlie MDM4 upregulation in cancer cells are largely unknown. Here, we have shown that this key oncogenic event mainly depends on a specific alternative splicing switch. We determined that while a nonsense-mediated, decay-targeted isoform of MDM4 (MDM4-S) is produced in normal adult tissues as a result of exon 6 skipping, enhanced exon 6 inclusion leads to expression of full-length MDM4 in a large number of human cancers. Although this alternative splicing event is likely regulated by multiple splicing factors, we identified the SRSF3 oncoprotein as a key enhancer of exon 6 inclusion. In multiple human melanoma cell lines and in melanoma patient-derived xenograft (PDX) mouse models, antisense oligonucleotide-mediated (ASO-mediated) skipping of exon 6 decreased MDM4 abundance, inhibited melanoma growth, and enhanced sensitivity to MAPK-targeting therapeutics. Additionally, ASO-based MDM4 targeting reduced diffuse large B cell lymphoma PDX growth. As full-length MDM4 is enhanced in multiple human tumors, our data indicate that this strategy is applicable to a wide range of tumor types. We conclude that enhanced MDM4 exon 6 inclusion is a common oncogenic event and has potential as a clinically compatible therapeutic target.
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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.