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CD95L mRNA is toxic to cells [SmallRNA_CD95L.50hrs.Drosha_ko]

ABSTRACT: >80% of a large number of tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death that is characterized by the simultaneous activation of multiple death pathways and preferentially affects transformed and cancer stem cells. We now show that 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 also provide evidence showing that the full length CD95L mRNA is also toxic and produces small Ago-associated RNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102779 | GEO | 2018/09/20

REPOSITORIES: GEO

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CD95L mRNA is toxic to cells

Project description:>80% of a large number of tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death that is characterized by the simultaneous activation of multiple death pathways and preferentially affects transformed and cancer stem cells. We now show that 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 also provide evidence showing that the full length CD95L mRNA is also toxic and produces small Ago-associated RNAs.

2018-09-21 | GSE114425 | GEO

CD95L mRNA is toxic to cells [SmallRNA_AGOpulldownCD95L_50hrs_HeyA8_CD95KO]

2018-09-20 | GSE102777 | GEO

CD95L mRNA is toxic to cells [SmallRNA.CD95L.50hrs.HeyA8]

2018-09-20 | GSE102780 | GEO

CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [AGOpulldownRNAseq.sm]

2017-09-16 | GSE101166 | GEO

CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [FasLRNAseq.lg]

2017-09-16 | GSE101232 | GEO

CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [shL3.shR6.RNAseq.lg]

Project description:The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. However, most siRNAs or shRNAs targeting either CD95 or CD95L induce DICE (Death Induced by CD95/CD95L Elimination), a form of cell death in which a combination of different cell death pathways are activated, that is selective for transformed cells, and that preferentially affects cancer stem cells. We now provide evidence that both CD95 and CD95L are part of a network of genes that contain sequences that when expressed as either siRNAs or shRNAs are toxic to cancer cells. They act through canonical RNAi by targeting the 3'UTRs of critical survival genes. We propose that these embedded toxic sequences are part of a conserved mechanism that regulates cell death, and we predict the existence of endogenous siRNAs, that when produced, induce cell death to regulate genome fidelity. Our data have implications for cancer therapy and the use of RNAi.

2017-09-16 | GSE101234 | GEO

CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [shL3.shR6.RNAseq.sm]

2017-09-16 | GSE101183 | GEO

CD95L derived si- and shRNAs and the CD95L mRNA kill cancer cells through an RNAi mechanism by targeting survival genes [siL3.RNAseq.lg]

Project description:We provide evidence that shRNAs and siRNAs derived from CD95 and CD95L preferentially target the 3' UTRs of survival genes culminating in a very robust mode of cell death we call DISE (Death Induced by Survival gene Elimination)

2017-09-16 | GSE101167 | GEO

CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [shL1.RNAseq.lg]

2017-09-16 | GSE101157 | GEO

Expression data from mNSc after 48 hour of treatment with CD95L-T4

Project description:In neural stem cells, stimulation of the â??death receptorâ?? CD95 does not trigger apoptosis but resulted in increased stem cell survival and neuronal specification via activation of the Src /PI3K /AKT/mTOR signalling pathway. To further characterize CD95-dependent neural stem cell survival and differentiation we used conventional gene expression profiling combined with translation state array analysis. Mouse neural stem cells grown in neurosphere cultures were stimulated with a trimerized CD95L construct (CD95L-T4) and total as well as polysomal bound RNA was isolated 48 hours after stimulation and analysed by microarrays. CD95L-T4 treatment induced a global increase in ribosome-bound mRNA and protein translation as well as changes on genes involved in neurogenesis, protein synthesis and transcription factors. Mouse neural stem cells grown in neurosphere cultures were stimulated with a trimerized CD95L construct (CD95L-T4) and total as well as polysomal bound RNA was isolated 48 hours after stimulation and hybridized on affymetrix microarrays.

2010-03-09 | E-GEOD-15623 | biostudies-arrayexpress

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