RT Journal Article
SR Electronic
T1 CD95L derived si- and shRNAs and the CD95L mRNA kill cancer cells through an RNAi mechanism by targeting survival genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 141952
DO 10.1101/141952
A1 William Putzbach
A1 Quan Q. Gao
A1 Monal Patel
A1 Aishe A. Sarshad
A1 Abbas Hadji
A1 Stijn van Dongen
A1 Ashley Haluck-Kangas
A1 Elizabeth Bartom
A1 Austin Stults
A1 Abdul S. Qadir
A1 Kwang-Youn A. Kim
A1 Markus Hafner
A1 Jonathan C. Zhao
A1 Andrea E. Murmann
A1 Marcus E. Peter
YR 2017
UL http://biorxiv.org/content/early/2017/06/16/141952.abstract
AB >80% of a large number of 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. By testing 4666 shRNAs derived from the CD95 and CD95L mRNAs and an unrelated control gene, Venus, we have located the most toxic sequences in the open reading frame of CD95L. Consistently, CD95L mRNA is highly toxic to cancer cells after complete deletion of CD95. Our data provide the first evidence for mRNAs to affect cell fate through RNAi in mammalian cells. In addition, they suggest that cancer cells can be targeted with specific toxic RNAi active sequences present in the genome.