An off-target nucleostemin RNAi inhibits growth in human glioblastoma-derived cancer stem cells
Entity
UAM. Departamento de Biología MolecularPublisher
Public Library of ScienceDate
2011-12-12Citation
10.1371/journal.pone.0028753
Plos One 6.12 (2011): e28753
ISSN
1932-6203 (online)DOI
10.1371/journal.pone.0028753Funded by
This work was supported by funds from: Ministerio de Ciencia e Innovación (SAF 2009-07259) Spain, and Fundación Eugenio Rodriguez Pascual (Madrid). The Centro de Biología Molecular S.O. is also the recipient of an institutional grant from the Ramón Areces Foundation. JG-R was the recipient of a predoctoral fellowship from the Gobierno Vasco, SpainSubjects
Apoptosis; Glioblastoma; RNA Interference; Cell Line, Tumor; Biología y Biomedicina / BiologíaRights
© 2011 Gil-Ranedo et al.Abstract
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
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Google Scholar:Gil-Ranedo, Jon
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Mendiburu-Eliçabe, Marina
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García-Villanueva, Mercedes
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Medina, Diego
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del Álamo, Marta
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Izquierdo, Marta
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