ArticleNature communications2018
6mer seed toxicity in tumor suppressive microRNAs.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Developing a pan cancer therapy based on DISE-inducing short RNAs.Molecular therapy. Nucleic acids · 2026Article
- Development of a DUX4-targeting antibody oligonucleotide conjugate as a therapy for FSHD.Nucleic acids research · 2026Article
- Liposome-Mediated MicroRNA Delivery: An Additional Layer of Gene Network Regulation and Nuclear ReprogrammingIranian biomedical journal · 2024Article
- 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
- Cancer kill code extension.Molecular therapy. Nucleic acids · 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
- Identification of potential target genes inNon-coding RNA 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
- 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
- The Ratio of Toxic-to-Nontoxic miRNAs Predicts Platinum Sensitivity in Ovarian Cancer.Cancer research · 2021Article
- Seed-mediated RNA interference of androgen signaling and survival networks induces cell death in prostate cancer cells.Molecular therapy. Nucleic acids · 2021Article
- AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.Molecular therapy. Nucleic acids · 2021Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Many small-interfering (si)RNAs are toxic to cancer cells through a 6mer seed sequence (positions 2-7 of the guide strand). Here we performed an siRNA screen with all 4096 6mer seeds revealing a preference for guanine in positions 1 and 2 and a high overall G or C content in the seed of the most toxic siRNAs for four tested human and mouse cell lines. Toxicity of these siRNAs stems from targeting survival genes with C-rich 3'UTRs. The master tumor suppressor miRNA miR-34a-5p is toxic through such a G-rich 6mer seed and is upregulated in cells subjected to genotoxic stress. An analysis of all mature miRNAs suggests that during evolution most miRNAs evolved to avoid guanine at the 5' end of the 6mer seed sequence of the guide strand. In contrast, for certain tumor-suppressive miRNAs the guide strand contains a G-rich toxic 6mer seed, presumably to eliminate cancer cells.
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Registered trials
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