ArticleThe Journal of biological chemistry2015
Transfected poly(I:C) activates different dsRNA receptors, leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 119 citations in OpenAlex.
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- Toll-like Receptor 3 as a Context-Dependent Molecular Switch in Epithelial Cancers: Balancing Cell Death and Tumor-Supportive Programs.International journal of molecular sciences · 2026Review
- A novel two-hit murine model of viral-primed sepsis-associated acute kidney injury.American journal of physiology. Renal physiology · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Poly(I:C) Lipoamino Bundle LNPs Induce Tumor Cytotoxicity and Immune Activation with Enhanced Efficacy by Survivin Silencing.International journal of molecular sciences · 2026Article
- Triplet RNA Lipid Nanoparticles for Locoregional Cancer Immunotherapy.Small science · 2026Article
- Targeting pattern recognition receptors for cancer therapy: Mechanisms and strategies.Acta pharmaceutica Sinica. B · 2025Review
- The Chromosome 19 miRNA cluster guards trophoblasts against overacting innate immunity.Communications biology · 2025Article
- Reconstitution of interferon regulatory factor 7 expression restores interferon beta induction in Huh7 cells.Journal of virology · 2025Article
- Synthetic RIG-I-Agonist RNA Induces Death of Hepatocellular Carcinoma Cells.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- Epigenetic activation of CD274/PD-L1 by the MSL complex expands its role beyond dosage compensation.Frontiers in immunology · 2025Article
- Poly (I:C)-induced inflammation requires the activation of toll-like receptor 3/CaTheranostics · 2025Article
- Junctophilin-2 is a double-stranded RNA-binding protein that regulates cardiomyocyte-autonomous innate immune response.Biochemical and biophysical research communications · 2024Article
- Machine learning-based integration develops a mitophagy-related lncRNA signature for predicting the progression of prostate cancer: a bioinformatic analysis.Discover oncology · 2024Article
- A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors.Cancer research · 2024Article
- Induction of apoptosis by double-stranded RNA was present in the last common ancestor of cnidarian and bilaterian animals.PLoS pathogens · 2024Article
- Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Messenger RNA Therapy for Female Reproductive Health.Molecular pharmaceutics · 2024Review
- SARS-CoV-2 variant-specific differences in inhibiting the effects of the PKR-activated integrated stress response.Virus research · 2024Article
- Exploiting the Zebrafish Model for Sepsis Research: Insights into Pathophysiology and Therapeutic Potentials.Drug design, development and therapy · 2024Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the effectiveness of surgery or radiation therapy for the treatment of early-stage prostate cancer (PCa), there is currently no effective strategy for late-stage disease. New therapeutic targets are emerging; in particular, dsRNA receptors Toll-like receptor 3 (TLR3) and cytosolic helicases expressed by cancer cells, once activated, exert a pro-apoptotic effect in different tumors. We previously demonstrated that the synthetic analog of dsRNA poly(I:C) induces apoptosis in the androgen-dependent PCa cell line LNCaP in a TLR3-dependent fashion, whereas only a weak apoptotic effect is observed in the more aggressive and androgen-independent PCa cells PC3 and DU145. In this paper, we characterize the receptors and the signaling pathways involved in the remarkable apoptosis induced by poly(I:C) transfected by Lipofectamine (in-poly(I:C)) compared with the 12-fold higher free poly(I:C) concentration in PC3 and DU145 cells. By using genetic inhibition of different poly(I:C) receptors, we demonstrate the crucial role of TLR3 and Src in in-poly(I:C)-induced apoptosis. Therefore, we show that the increased in-poly(I:C) apoptotic efficacy is due to a higher binding of endosomal TLR3. On the other hand, we show that in-poly(I:C) binding to cytosolic receptors MDA5 and RIG-I triggers IRF3-mediated signaling, leading uniquely to the up-regulation of IFN-β, which likely in turn induces increased TLR3, MDA5, and RIG-I proteins. In summary, in-poly(I:C) activates two distinct antitumor pathways in PC3 and DU145 cells: one mediated by the TLR3/Src/STAT1 axis, leading to apoptosis, and the other one mediated by MDA5/RIG-I/IRF3, leading to immunoadjuvant IFN-β expression.
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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.