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| Status |
Public on Oct 21, 2011 |
| Title |
Transcriptional effect of an off-target shRNA targeting nucleostemin in human glioblastoma-derived cancer stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Glioblastomas (GBM) may contain a variable proportion of active cancer stem cells (CSCs) capable of self-renewal, of aggregating into CD133+ neurospheres, and to develop intracranial tumors that phenocopy the original ones. We hypothesized that nucleostemin may contribute to cancer stem cell biology as these cells share characteristics with normal stem cells. Here we report that nucleostemin is expressed in GBM-CSCs isolated from patient samples. The significance of its expression was addressed by targeting the corresponding mRNA using lentivirally transduced short hairpin RNA (shRNA). We found that an off-target nucleostemin RNAi (shRNA22) abolishes proliferation and induces apoptosis in GBM-CSCs. Furthermore, in the presence of shRNA22, GBM-CSCs failed to form neurospheres in vitro or grow on soft agar. When these cells are xenotransplanted into the brains of nude rats, tumor development is severely compromised. Attempts were made to identify the primary target of shRNA22, suggesting a transcription factor involved in one of the MAP-kinases signaling-pathways. The use of this shRNA may offer a new therapeutic approach for this incurable type of brain tumors.
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| Overall design |
The transcriptional profile of neurosphere cultures infected with lentiviral particles containing shRNA22 was compared with the profile of neurosphere cultures infected with lentiviral particles containing control shRNA. Experiments were done in triplicate.
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| Contributor(s) |
Gil-Ranedo J, Izquierdo Rojo M |
| Citation missing |
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| Submission date |
Jul 06, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Jon Gil-Ranedo |
| Organization name |
CBMSO
|
| Street address |
C/ Nicolás Cabrera nº1, CBMSO, lab 224
|
| City |
Madrid |
| State/province |
Madrid |
| ZIP/Postal code |
28029 |
| Country |
Spain |
| |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (6)
|
| GSM755164 |
cells treated with the shRNA22, biological replicate 1 |
| GSM755165 |
cells treated with the shRNA22, biological replicate 2 |
| GSM755166 |
cells treated with the shRNA22, biological replicate 3 |
| GSM755167 |
cells treated with the shRNA control, biological replicate 1 |
| GSM755168 |
cells treated with the shRNA control, biological replicate 2 |
| GSM755169 |
cells treated with the shRNA control, biological replicate 3 |
|
| Relations |
| BioProject |
PRJNA143277 |
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