ArticleProceedings of the National Academy of Sciences of the United States of America2020
RNA-binding protein DDX3 mediates posttranscriptional regulation of androgen receptor: A mechanism of castration resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Molecular insights into DDX3X-androgen receptor mRNA regulation via non-canonical G-quadruplex in castration-resistant prostate cancer.Oncogene · 2026Article
- Transcriptional analyses identify pericyte-centered signaling programs altered by sex and brain region in Alzheimer's Disease.Communications biology · 2026Article
- The human DEAD-box protein DDX3X regulates host and viral mRNA translation during Sendai Virus infection.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic insights and clinical implications of RNA-binding proteins in prostate cancer.Discover oncology · 2026Review
- The role of LLPS of biomacromolecules in the gonads and related diseases.Frontiers in endocrinology · 2026Review
- Targeting androgen receptor signaling to enhance cancer immunotherapy.Trends in pharmacological sciences · 2025Review
- Targeting DDX3X suppresses progression of KRAS-driven lung cancer by disrupting antioxidative homeostasis and inducing ferroptosis.Cell death & disease · 2025Article
- Prostatic androgen receptor signaling shows an age-related and lobe-specific alteration in mice.Scientific reports · 2024Article
- Epigenetic reader ZMYND11 noncanonical function restricts HNRNPA1-mediated stress granule formation and oncogenic activity.Signal transduction and targeted therapy · 2024Article
- The RNA secondary structure of androgen receptor-FL and V7 transcripts reveals novel regulatory regions.Nucleic acids research · 2024Article
- Review
- Integrating intracellular and extracellular proteomic profiling for in-depth investigations of cellular communication in a model of prostate cancer.Proteomics · 2023Article
- Article
- Noncoding RNA circBtnl1 suppresses self-renewal of intestinal stem cells via disruption of Atf4 mRNA stability.The EMBO journal · 2023Article
- Regulation of AR mRNA translation in response to acute AR pathway inhibition.Nucleic acids research · 2022Article
- The human DEAD-box helicase DDX3X as a regulator of mRNA translation.Frontiers in cell and developmental biology · 2022Review
- Androgen receptor signaling and spatial chromatin organization in castration-resistant prostate cancer.Frontiers in medicine · 2022Review
- The androgen receptor messenger RNA: what do we know?RNA biology · 2022Review
- Cytoplasmic DDX3 as prognosticator in male breast cancer.Virchows Archiv : an international journal of pathology · 2021Article
- DDX52 knockdown inhibits the growth of prostate cancer cells by regulating c-Myc signaling.Cancer cell international · 2021Article
Corrections and comments
- Commented on byUro-Science.2021
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Prostate cancer (CaP) driven by androgen receptor (AR) is treated with androgen deprivation; however, therapy failure results in lethal castration-resistant prostate cancer (CRPC). AR-low/negative (ARL/-) CRPC subtypes have recently been characterized and cannot be targeted by hormonal therapies, resulting in poor prognosis. RNA-binding protein (RBP)/helicase DDX3 (DEAD-box helicase 3 X-linked) is a key component of stress granules (SG) and is postulated to affect protein translation. Here, we investigated DDX3-mediated posttranscriptional regulation of AR mRNA (messenger RNA) in CRPC. Using patient samples and preclinical models, we objectively quantified DDX3 and AR expression in ARL/- CRPC. We utilized CRPC models to identify DDX3:AR mRNA complexes by RNA immunoprecipitation, assess the effects of DDX3 gain/loss-of-function on AR expression and signaling, and address clinical implications of targeting DDX3 by assessing sensitivity to AR-signaling inhibitors (ARSI) in CRPC xenografts in vivo. ARL/- CRPC expressed abundant AR mRNA despite diminished levels of AR protein. DDX3 protein was highly expressed in ARL/- CRPC, where it bound to AR mRNA. Consistent with a repressive regulatory role, DDX3 localized to cytoplasmic puncta with SG marker PABP1 in CRPC. While induction of DDX3-nucleated SGs resulted in decreased AR protein expression, inhibiting DDX3 was sufficient to restore 1) AR protein expression, 2) AR signaling, and 3) sensitivity to ARSI in vitro and in vivo. Our findings implicate the RBP protein DDX3 as a mechanism of posttranscriptional regulation for AR in CRPC. Clinically, DDX3 may be targetable for sensitizing ARL/- CRPC to AR-directed therapies.
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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.