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.
journal_name
Elifejournal_title
eLifeauthors
Putzbach W,Gao QQ,Patel M,van Dongen S,Haluck-Kangas A,Sarshad AA,Bartom ET,Kim KA,Scholtens DM,Hafner M,Zhao JC,Murmann AE,Peter MEdoi
10.7554/eLife.29702subject
Has Abstractpub_date
2017-10-24 00:00:00issn
2050-084Xjournal_volume
6pub_type
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