RT Journal Article
T1 An Off-Target Nucleostemin RNAi Inhibits Growth in Human Glioblastoma-Derived Cancer Stem Cells
A1 Gil Ranedo, Jon
A1 Mendiburu-Eliçabe Garganta, Marina
A1 García Villanueva, Mercedes
A1 Medina López, Diego
A1 Álamo De Pedro, Marta del
A1 Izquierdo Rojo, Marta
A2 Keith L. Black, 
AB 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, and that its expression, conversely to what it has been described for ordinary stem cells, does not disappear when cells are differentiated. The significance of nucleostemin expression in CSCs was addressed by targeting the corresponding mRNA using lentivirally transduced short hairpin RNA (shRNA). In doing so, we found an off-target nucleostemin RNAi (shRNA22) that 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 significantly delayed. Attempts were made to identify the primary target/s of shRNA22, suggesting a transcription factor involved in one of the MAP-kinases signaling-pathways or multiple targets. The use of this shRNA may contribute to develop new therapeutic approaches for this incurable type of brain tumor.
YR 2011
FD 2011-12-12
LK https://hdl.handle.net/20.500.14352/100496
UL https://hdl.handle.net/20.500.14352/100496
LA eng
NO Gil-Ranedo J, Mendiburu-Eliçabe M, García-Villanueva M, Medina D, Del Álamo M, Izquierdo M. An Off-Target Nucleostemin RNAi Inhibits Growth in Human Glioblastoma-Derived Cancer Stem Cells. PLoS ONE 2011;6:e28753. https://doi.org/10.1371/journal.pone.0028753.
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Fundación Eugenio Rodríguez Pascual
NO Fundación Ramón Areces
NO Gobierno Vasco
DS Docta Complutense
RD 9 abr 2025