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| Status |
Public on Sep 16, 2017 |
| Title |
CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes [shL3.shR6.RNAseq.sm] |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
293T (shL3 site deleted) cells were infected with either pTIP-shScr or pTIP-shL3 and following puromycin selection small RNAs were analyzed by deep sequencing 50 or 100hrs after addition of doxycycline/HeyA8 (shR6 site deleted) cells were infected with either pLKO-shScr or pLKO-shR6 and following puromycin selection small RNAs were analyzed by deep sequencing 50 or 100hrs after addition of selection.
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| Contributor(s) |
Putzbach W, Peter ME, Bartom E |
| Citation(s) |
29063830 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R35 CA197450 |
DISE - a natural cancer surveillance mechanism - a new road to cancer therapy |
NORTHWESTERN UNIVERSITY AT CHICAGO |
Marcus E. Peter |
|
| Submission date |
Jul 11, 2017 |
| Last update date |
Sep 08, 2022 |
| Contact name |
Marcus Peter |
| E-mail(s) |
m-peter@northwestern.edu
|
| Organization name |
Northwestern University Feinberg School of Medicine
|
| Street address |
303 East Superior Street, Lurie 6-123
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (16)
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| GSM2700168 |
293T pTIP-L3 50hrs (duplicate 2) |
| GSM2700169 |
293T pTIP-scr 100hrs (duplicate 1) |
| GSM2700170 |
293T pTIP-scr 100hrs (duplicate 2) |
| GSM2700171 |
293T pTIP-L3 100hrs (duplicate 1) |
| GSM2700172 |
293T pTIP-L3 100hrs (duplicate 2) |
| GSM2700173 |
HeyA8 R6 KO C11 pLKO-scr 50hrs (duplicate 1) |
| GSM2700174 |
HeyA8 R6 KO C11 pLKO-scr 50hrs (duplicate 2) |
| GSM2700175 |
HeyA8 R6 KO C11 pLKO-R6 50hrs (duplicate 1) |
| GSM2700176 |
HeyA8 R6 KO C11 pLKO-R6 50hrs (duplicate 2) |
| GSM2700177 |
HeyA8 R6 KO C11 pLKO-scr 100hrs (duplicate 1) |
| GSM2700178 |
HeyA8 R6 KO C11 pLKO-scr 100hrs (duplicate 2) |
| GSM2700179 |
HeyA8 R6 KO C11 pLKO-R6 100hrs (duplicate 1) |
| GSM2700180 |
HeyA8 R6 KO C11 pLKO-R6 100hrs (duplicate 2) |
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| This SubSeries is part of SuperSeries: |
| GSE87817 |
CD95L derived si- and shRNAs kill cancer cells through an RNAi mechanism by targeting survival genes |
|
| Relations |
| BioProject |
PRJNA393852 |
| SRA |
SRP111544 |
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