ArticleScientific reports2022
Identification of the toxic 6mer seed consensus for human cancer cells.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Developing a pan cancer therapy based on DISE-inducing short RNAs.Molecular therapy. Nucleic acids · 2026Article
- Important Aspects of siRNA Design for Optimal Efficacy In Vitro and In Vivo.International journal of cell biology · 2025Review
- Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer's disease and aging.Nature communications · 2024Article
- DISE, an ancient anti-cancer mechanism that senses mutational load in cancerous cells?Oncotarget · 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
- Therapeutic siRNA: State-of-the-Art and Future Perspectives.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- SPOROS: A pipeline to analyze DISE/6mer seed toxicity.PLoS computational biology · 2022Article
- DISE/6mer seed toxicity-a powerful anti-cancer mechanism with implications for other diseases.Journal of experimental & clinical cancer research : CR · 2021Review
- The Ratio of Toxic-to-Nontoxic miRNAs Predicts Platinum Sensitivity in Ovarian Cancer.Cancer research · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
6mer seed toxicity is a novel cell death mechanism that kills cancer cells by triggering death induced by survival gene elimination (DISE). It is based on si- or shRNAs with a specific G-rich nucleotide composition in position 2-7 of their guide strand. An arrayed screen of 4096 6mer seeds on two human and two mouse cell lines identified G-rich 6mers as the most toxic seeds. We have now tested two additional cell lines, one human and one mouse, identifying the GGGGGC consensus as the most toxic average 6mer seed for human cancer cells while slightly less significant for mouse cancer cells. RNA Seq and bioinformatics analyses suggested that an siRNA containing the GGGGGC seed (siGGGGGC) is toxic to cancer cells by targeting GCCCCC seed matches located predominantly in the 3' UTR of a set of genes critical for cell survival. We have identified several genes targeted by this seed and demonstrate direct and specific targeting of GCCCCC seed matches, which is attenuated upon mutation of the GCCCCC seed matches in these 3' UTRs. Our data show that siGGGGGC kills cancer cells through its miRNA-like activity and points at artificial miRNAs, si- or shRNAs containing this seed as a potential new cancer therapeutics.
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Registered trials
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