ArticleCell reports2024
XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells.
Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 12 citations in OpenAlex.
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Engineered targeted enhancement of translation in mammalian cell.BMC biology · 2026Article
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- A spring-loaded grip-and-pull mechanism for stepwise RNA duplex unwinding by Xrn1.Nucleic acids research · 2026Article
- Inducing tumor-intrinsic innate immune response to break cancer immunotherapy resistance.Frontiers in medicine · 2026Review
- ZYS-1 is not an ADAR1 inhibitor.RNA (New York, N.Y.) · 2025Article
- Spliceosome inhibition induces Z-RNA and ZBP1-driven cell death in small cell lung cancer.Cell reports · 2025Article
- PACT suppresses PKR activation through dsRNA binding and dimerization, and is a therapeutic target for triple-negative breast cancer.RNA (New York, N.Y.) · 2025Article
- Uridine as a hub in cancer metabolism and RNA biology.Experimental & molecular medicine · 2025Review
- Unleashing viral mimicry: A combinatorial strategy to enhance the efficacy of PARP7 inhibitors.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Mitophagy-Related Gene CHDH Predicts Prognosis and Immune Response and Inhibits Proliferation and Migration in vitro and in vivo of Oral Squamous Cell Carcinoma.Journal of inflammation research · 2025Article
- ADAR1: from basic mechanisms to inhibitors.Trends in cell biology · 2025Review
- RNA-binding proteins and exoribonucleases modulating miRNA in cancer: the enemy within.Experimental & molecular medicine · 2024Review
- Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer.Cell reports · 2024Article
- The competitive landscape of the dsRNA world.Molecular cell · 2024Review
Corrections and comments
- Erratum issued
- Update of
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Emerging data suggest that induction of viral mimicry responses through activation of double-stranded RNA (dsRNA) sensors in cancer cells is a promising therapeutic strategy. One approach to induce viral mimicry is to target molecular regulators of dsRNA sensing pathways. Here, we show that the exoribonuclease XRN1 is a negative regulator of the dsRNA sensor protein kinase R (PKR) in cancer cells with high interferon-stimulated gene expression. XRN1 deletion causes PKR pathway activation and consequent cancer cell lethality. Disruption of interferon signaling with the JAK1/2 inhibitor ruxolitinib can decrease cellular PKR levels and rescue sensitivity to XRN1 deletion. Conversely, interferon-β stimulation can increase PKR levels and induce sensitivity to XRN1 inactivation. Lastly, XRN1 deletion causes accumulation of endogenous complementary sense/anti-sense RNAs, which may represent candidate PKR ligands. Our data demonstrate how XRN1 regulates PKR and how this interaction creates a vulnerability in cancer cells with an activated interferon cell state.
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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.