ArticleeLife2017
Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 66 citations in OpenAlex.
- Developing a pan cancer therapy based on DISE-inducing short RNAs.Molecular therapy. Nucleic acids · 2026Article
- Frameworks for transformational breakthroughs in RNA-based medicines.Nature reviews. Drug discovery · 2024Review
- Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer's disease and aging.Nature communications · 2024Article
- Construction of a Set of Novel Transposon Vectors for Efficient Silencing of Protein and lncRNA Genes via CRISPR Interference.Molecular biotechnology · 2023Article
- DISE, an ancient anti-cancer mechanism that senses mutational load in cancerous cells?Oncotarget · 2023Article
- An unbiased seed-based RNAi selection screen identifies small RNAs that inhibit androgen signaling and prostate cancer cell growth.Molecular therapy. Nucleic acids · 2023Article
- Analysis of the Contribution of 6-mer Seed Toxicity to HIV-1-Induced Cytopathicity.Journal of virology · 2023Article
- CD95/Fas ligand mRNA is toxic to cells through more than one mechanism.Molecular biomedicine · 2023Article
- CD95/Fas ligand induced toxicity.Biochemical Society transactions · 2023Article
- The length of uninterrupted CAG repeats in stem regions of repeat disease associated hairpins determines the amount of short CAG oligonucleotides that are toxic to cells through RNA interference.Cell death & disease · 2022Article
- G-rich motifs within phosphorothioate-based antisense oligonucleotides (ASOs) drive activation of FXN expression through indirect effects.Nucleic acids research · 2022Article
- Identification of the toxic 6mer seed consensus for human cancer cells.Scientific reports · 2022Article
- shRNAs targeting mouse Adam10 diminish cell response to proinflammatory stimuli independently of Adam10 silencing.Biology open · 2022Article
- SPOROS: A pipeline to analyze DISE/6mer seed toxicity.PLoS computational biology · 2022Article
- Specificity of oligonucleotide gene therapy (OGT) agents.Theranostics · 2022Review
- The dual role of the CD95 and CD95L signaling pathway in glioblastoma.Frontiers in immunology · 2022Review
- DISE/6mer seed toxicity-a powerful anti-cancer mechanism with implications for other diseases.Journal of experimental & clinical cancer research : CR · 2021Review
- Non-targeting control for MISSION shRNA library silencesMolecular therapy. Nucleic acids · 2021Article
- CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells.iScience · 2021Article
- AGO CLIP-based imputation of potent siRNA sequences targeting SARS-CoV-2 with antifibrotic miRNA-like activity.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3'UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that specific toxic RNAi-active sequences present in the genome can kill cancer cells.
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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.