An Off-Target Nucleostemin RNAi Inhibits Growth in Human Glioblastoma-Derived Cancer Stem Cells

Gil-Ranedo, Jon; Mendiburu-Eliçabe, Marina; García-Villanueva, Mercedes; Medina, Diego L.; Álamo, Marta del; Izquierdo, Marta López

doi:10.1371/journal.pone.0028753

Cited by 16 publications

(19 citation statements)

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“…26 What's more, the differentiated cells do not loose expression of this protein, despite not expressing any other stemness-related genes. 26 If it is expressed in human glioma cells and its expression is correlated with cancer progression, it may serve as a powerful prognostic marker for doctors. In the present study, we identified the positive relation between the expression of nucleostemin and Ki-67 in human glioma tissue and cell lines, and distinctly the depletion of nucleostemin reduced cell proliferation.…”

Section: Introductionmentioning

confidence: 98%

“…Nucleostemin has been identified to play a role in the self‐renewal of glioblastoma stem cells . What's more, the differentiated cells do not loose expression of this protein, despite not expressing any other stemness‐related genes . If it is expressed in human glioma cells and its expression is correlated with cancer progression, it may serve as a powerful prognostic marker for doctors.…”

Section: Introductionmentioning

confidence: 99%

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Nucleostemin promotes the proliferation of human glioma via Wnt/β‐Catenin pathway

et al. 2015

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Nucleostemin, nucleolar guanosine triphosphate (GTP)-binding protein 3, is a member of the MMR1/HSR1 GTP-binding protein family. The important roles of nucleostemin in self-renewal, cell cycle regulation, apoptosis, and cell proliferation of various cancer types as been shown. Nevertheless, its expression and potential functions in human glioma is still unclear. In the present study, we demonstrated that up-regulation of nucleostemin was tightly related to poor 5-year-survival ratios. In serum-starved and re-feeding models of U251 and U373MG, we observed the rising expression of nucleostemin and p-β-Catenin (p-Tyr645) were accompanied with cell proliferation markers (cyclin D1 and proliferating cell nuclear antigen (PCNA)). Employing nucleostemin-depletion models, we found down-regulated nucleostemin and p-β-Catenin. The flow cytometry analysis proved the weakened cell proliferation. Moreover, we detected the translocation of β-Catenin into the nucleus was impaired, meaning the inhibition of the Wnt/β-Catenin pathway. Taken together, we identified a positive correlation between up-regulation of nucleostemin and human glioma cell proliferation and that knocking-down nucleostemin alleviated glioma proliferation by reducing β-Catenin transportation into the nucleus. All results suggested that nucleostemin might accelerate human glioma proliferation via the Wnt/β-Catenin pathway.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Nucleostemin promotes the proliferation of human glioma via Wnt/β‐Catenin pathway

et al. 2015

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“…In addition, according to previous studies, the miRNAs we identified are related to glioblastoma. For example, it was found that “has-miR-9” inhibit differentiation of glioblastoma stem cells, and the calmodulin-binding transcription activator 1 (CAMTA1) as “has-miR-9” target is a tumor suppressor in glioblastoma [37]. …”

Section: Conclusion and Discussionmentioning

confidence: 99%

Subtyping glioblastoma by combining miRNA and mRNA expression data using compressed sensing-based approach

Tang

Duan

Zhang

et al. 2013

J Bioinform Sys Biology

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In the clinical practice, many diseases such as glioblastoma, leukemia, diabetes, and prostates have multiple subtypes. Classifying subtypes accurately using genomic data will provide individualized treatments to target-specific disease subtypes. However, it is often difficult to obtain satisfactory classification accuracy using only one type of data, because the subtypes of a disease can exhibit similar patterns in one data type. Fortunately, multiple types of genomic data are often available due to the rapid development of genomic techniques. This raises the question on whether the classification performance can significantly be improved by combining multiple types of genomic data. In this article, we classified four subtypes of glioblastoma multiforme (GBM) with multiple types of genome-wide data (e.g., mRNA and miRNA expression) from The Cancer Genome Atlas (TCGA) project. We proposed a multi-class compressed sensing-based detector (MCSD) for this study. The MCSD was trained with data from TCGA and then applied to subtype GBM patients using an independent testing data. We performed the classification on the same patient subjects with three data types, i.e., miRNA expression data, mRNA (or gene expression) data, and their combinations. The classification accuracy is 69.1% with the miRNA expression data, 52.7% with mRNA expression data, and 90.9% with the combination of both mRNA and miRNA expression data. In addition, some biomarkers identified by the integrated approaches have been confirmed with results from the published literatures. These results indicate that the combined analysis can significantly improve the accuracy of classifying GBM subtypes and identify potential biomarkers for disease diagnosis.

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“…Reduction in Nanog‐1 expression in breast CSCs by 3‐O‐methylfunicone inhibited sphere formation and colony formation (172). An off‐target shRNA against neostemin, lentivirally transfected into glioblastoma cells, led to preferential apoptosis of CD133 + putative CSCs and significantly slowed xenotransplanted tumor growth (173). Another study found shRNA knockdown of ubiquitine ligases to induce apoptosis and differentiation in cell line derived glioblastoma CSCs (174).…”

Section: Prognostic Value Of Cscs and Their Implications For Therapymentioning

confidence: 99%

The hitchhikers guide to cancer stem cell theory: Markers, pathways and therapy

2012

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Cancer stem cell (CSC) biology is a rapidly developing field within cancer research. CSCs are postulated to be a unique cell population exclusively capable of infinite self renewal, multilineage differentiation and with ability to evade conventional cytotoxic cancer therapy. These traits distinguish CSCs from their more differentiated counterparts, which possess only limited or no potential for self renewal and tumor initiation. Therefore, CSCs would be the driving motor of malignant growth and therapy resistance. Accordingly, successful cancer treatment would need to eliminate this highly potent group of cells, since even small residual numbers would suffice to recapitulate the disease after therapy. Putative CSCs has been identified in a broad range of human malignancies and several cell surface markers have been associated with their stem cell phenotype. Despite all efforts, a pure CSC population has not been isolated and often in vitro clonogenic and in vivo tumorigenic potential is found in several cell populations with occasionally contradictory surface marker signatures. Here, we give a brief overview of recent advances in CSC theory, including the signaling pathways in CSCs that also appear crucial for stem cells homeostasis in normal tissues. We discuss evidence for the interaction of CSCs with the stromal tumor environment. Finally, we review the emerging potentially effective CSC-targeted treatment strategies and their future role in therapy. ' 2012 International Society for Advancement of Cytometry Key termscancer stem cells; cancer stem cell markers; cancer stem cell niche; therapy resistance CANCER stem cell (CSC) theory hypothesizes that heterogeneity within tumors is not a mere consequence of random mutation and clonal evolution, but results from an intrinsic hierarchy of cells, with the putative CSC at the apex of the hierarchy (1,2). The CSC is thought to share several key features with normal stem cells: unlimited capacity for self renewal, including maintenance of the CSC population through asymmetric division, the ability to differentiate into several cell lineages and intrinsic resistance against cytotoxic therapies through drug-efflux mechanisms and slow cell cycling (2). CSC theory postulates that not all tumor cells are equal with regard to self-renewal, tumor initiation, and maintenance potential, these traits being reserved for the CSC population. Additionally, cellular heterogeneity and hierarchy within the tumor originates from CSCs, which give rise to daughter cells that proliferate and differentiate into the cell mass that compromises a significant portion of the bulk tumor (1). Further, CSCs are thought to be responsible for therapy resistance, minimal residual disease and relapse after initial successful therapy, their stem-like features making them able to evade conventional treatment modalities (3). It has also been implied that these stem cell traits allow CSCs to play a leading role in metastasis (4-6).Since the first experiments verifying that a specific phenotype wi...

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An Off-Target Nucleostemin RNAi Inhibits Growth in Human Glioblastoma-Derived Cancer Stem Cells

Cited by 16 publications

References 46 publications

Nucleostemin promotes the proliferation of human glioma via Wnt/β‐Catenin pathway

Nucleostemin promotes the proliferation of human glioma via Wnt/β‐Catenin pathway

Subtyping glioblastoma by combining miRNA and mRNA expression data using compressed sensing-based approach

The hitchhikers guide to cancer stem cell theory: Markers, pathways and therapy

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