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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE101234 | GEO | 2017/09/16

SECONDARY ACCESSION(S): PRJNA393938

REPOSITORIES: GEO