ArticleOncogene2016
RNA helicase DDX3: a novel therapeutic target in Ewing sarcoma.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed.
- Targeting the DDX3/PAF1 axis enhances chemotherapy efficacy in pancreatic ductal adenocarcinoma.Cancer letters · 2026Article
- Genetic and chromosomal dysregulations of progenitor cells in the etiology and pathogenesis of pediatric cancers.American journal of stem cells · 2026Review
- Targeting FAM134B-DDX3X axis inhibiting AKT signaling in hepatocellular carcinoma.Cell death & disease · 2025Article
- KPNA2 promotes osteosarcoma progression by regulating the alternative splicing of DDX3X mediated by YBX1.Oncogene · 2025Article
- Targeting DDX3X eliminates leukemia stem cells in chronic myeloid leukemia by blocking NT5DC2 mRNA translation.Oncogene · 2025Article
- Inhibiting the RNA helicase DDX3X in Burkitt lymphoma induces oxydative stress and impedes tumor progression in xenografts.Frontiers in cell and developmental biology · 2025Article
- DDX3 participates in miRNA biogenesis and RNA interference through translational control of PACT and interaction with AGO2.FEBS open bio · 2025Article
- EWS-FLI1 and Activator Protein-1 (AP-1) Reciprocally Regulate Extracellular-Matrix Proteins in Ewing sarcoma Cells.International journal of molecular sciences · 2024Article
- RNA helicase DDX3 regulates RAD51 localization and DNA damage repair in Ewing sarcoma.iScience · 2024Article
- Prokaryotic Expression and Affinity Purification of DDX3 Protein.Protein and peptide letters · 2024Article
- DHX9-mediated pathway contributes to the malignant phenotype of myelodysplastic syndromes.iScience · 2023Article
- Molecular docking, synthesis, and biological evaluation of 7-azaindole-derivative (7AID) as novel anti-cancer agent and potent DDX3 inhibitor:-an in silico and in vitro approach.Medical oncology (Northwood, London, England) · 2022Article
- DEAD-Box RNA Helicases DDX3X and DDX5 as Oncogenes or Oncosuppressors: A Network Perspective.Cancers · 2022Review
- Post-transcriptional regulation ofAutophagy · 2022Article
- Inhibition of DDX3 and COX-2 by forskolin and evaluation of anti-proliferative, pro-apoptotic effects on cervical cancer cells: molecular modelling and in vitro approaches.Medical oncology (Northwood, London, England) · 2022Article
- Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy.Frontiers in oncology · 2022Review
- The human DEAD-box helicase DDX3X as a regulator of mRNA translation.Frontiers in cell and developmental biology · 2022Review
- Targeting DDX3X Helicase Activity with BA103 Shows Promising Therapeutic Effects in Preclinical Glioblastoma Models.Cancers · 2021Article
- Arginine Methylation of hnRNPK Inhibits the DDX3-hnRNPK Interaction to Play an Anti-Apoptosis Role in Osteosarcoma Cells.International journal of molecular sciences · 2021Article
- Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
RNA helicase DDX3 has oncogenic activity in breast and lung cancers and is required for translation of complex mRNA transcripts, including those encoding key cell-cycle regulatory proteins. We sought to determine the expression and function of DDX3 in sarcoma cells, and to investigate the antitumor activity of a novel small molecule DDX3 inhibitor, RK-33. Utilizing various sarcoma cell lines, xenografts and human tissue microarrays, we measured DDX3 expression at the mRNA and protein levels, and evaluated cytotoxicity of RK-33 in sarcoma cell lines. To study the role of DDX3 in Ewing sarcoma, we generated stable DDX3-knockdown Ewing sarcoma cell lines using DDX3-specific small hairpin RNA (shRNA), and assessed oncogenic activity. DDX3-knockdown and RK-33-treated Ewing sarcoma cells were compared with wild-type cells using an isobaric mass-tag quantitative proteomics approach to identify target proteins impacted by DDX3 inhibition. Overall, we found high expression of DDX3 in numerous human sarcoma subtypes compared with non-malignant mesenchymal cells, and knockdown of DDX3 by RNA interference inhibited oncogenic activity in Ewing sarcoma cells. Treatment with RK-33 was preferentially cytotoxic to sarcoma cells, including chemotherapy-resistant Ewing sarcoma stem cells, while sparing non-malignant cells. Sensitivity to RK-33 correlated with DDX3 protein expression. Growth of human Ewing sarcoma xenografts expressing high DDX3 was inhibited by RK-33 treatment in mice, without overt toxicity. DDX3 inhibition altered the Ewing sarcoma cellular proteome, especially proteins involved in DNA replication, mRNA translation and proteasome function. These data support further investigation of the role of DDX3 in sarcomas, advancement of RK-33 to Ewing sarcoma clinical trials and development of RNA helicase inhibition as a novel anti-neoplastic strategy.
Indexed as
Identifiers
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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.