MicroRNAs and glioblastoma; the stem cell connection

Godlewski, Jakub; Newton, Herbert B.; Chiocca, E. Antonio; Lawler, Sean E.

doi:10.1038/cdd.2009.71

Cited by 92 publications

(71 citation statements)

References 78 publications

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“…23 Interestingly, some of these microRNAs have also been implicated in neural stem cells and neural development, thus intertwining stem cell biology and tumorigenesis. 25 Since Musashi1 is equally implicated in both processes, we believe that miRNAs, particularly tumor suppressor miRNAs, might play a role in its regulation. Moreover, the Msi1 mRNA has a long 3' untranslated region (1,797 nucleotides in length), making it an excellent candidate for miRNA regulation.…”

Section: Resultsmentioning

confidence: 99%

“…These miRNAs have decreased or no expression in brain tumors, as compared to normal brain tissue. 25 When their expression is restored in cancer cells these miRNAs can slow down cellular proliferation and promote neural differentiation; additionally, these miRNAs have also been linked to stem cell self-renewal.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…The dual roles of these tumor suppressor miRNAs implies an overlap between development and cancer. 25 We utilized a neuroblastic differentiation assay to monitor changes in both Msi1 and miRNA expression. In this assay, SK-N-BE neuroblastoma cells, which display high Msi1 expression, can be differentiated along the neuronal lineage using all-trans retinoic acid for a period of one week.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

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The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor miRNAs

Qiao

Smith

et al. 2011

RNA Biology

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Section: Resultsmentioning

confidence: 99%

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

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The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor miRNAs

Qiao

Smith

et al. 2011

RNA Biology

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“…Recent studies indicate that certain miRNAs (such as miR-124, miR-137, miR-128, and miR-7) function as tumor suppressors (19,49). These miRNAs are rarely expressed in gliomas; however, their overexpression restrains proliferation and self-renewal of glioma stem-like cells by promoting neural differentiation (20,21).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-146a Inhibits Glioma Development by Targeting Notch1

Mei

Bachoo²,

Zhang³

2011

Molecular and Cellular Biology

159

131

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Dysregulated epidermal growth factor receptor (EGFR) signaling through either genomic amplification or dominant-active mutation (EGFR vIII ), in combination with the dual inactivation of INK4A/ARF and PTEN, is a leading cause of gliomagenesis. Our global expression analysis for microRNAs revealed that EGFR activation induces miR-146a expression, which is further potentiated by inactivation of PTEN. Unexpectedly, overexpression of miR-146a attenuates the proliferation, migration, and tumorigenic potential of Ink4a/Arf ؊/؊ Pten ؊/؊ Egfr vIII murine astrocytes. Its ectopic expression also inhibits the glioma development of a human glioblastoma cell line in an orthotopic xenograft model. Such an inhibitory function of miR-146a on gliomas is largely through downregulation of Notch1, which plays a key role in neural stem cell maintenance and is a direct target of miR-146a. Accordingly, miR-146a modulates neural stem cell proliferation and differentiation and reduces the formation and migration of glioma stem-like cells. Conversely, knockdown of miR-146a by microRNA sponge upregulates Notch1 and promotes tumorigenesis of malignant astrocytes. These findings indicate that, in response to oncogenic cues, miR-146a is induced as a negative-feedback mechanism to restrict tumor growth by repressing Notch1. Our results provide novel insights into the signaling pathways that link neural stem cells to gliomagenesis and may lead to new strategies for treating brain tumors.Gliomas are the most frequently observed brain tumors, with glioblastoma multiforme (GBM) being the most common and aggressive form in adults (35). Despite major therapeutic improvements made by combining neurosurgery, chemotherapy, and radiotherapy, the prognosis and survival rate for patients with GBM is still extremely poor (7). The deadly nature of GBM originates from explosive growth and invasive behavior, which are fueled by dysregulation of multiple signaling pathways. Epidermal growth factor receptor (EGFR) activation, in cooperation with loss of tumor suppressor functions, such as mutations in Ink4a/Arf and Pten genes, constitutes a lesion signature for GBM (4). Such dysregulated genetic pathways are sufficient to transform neural stem cells (NSCs) or astrocytes into cancer stem-like cells. This gives rise to highgrade malignant gliomas with a pathological phenotype resembling human GBM (5, 59). However, the downstream events underlying these genetic dysregulations in gliomagenic cells have not been fully elucidated.MicroRNAs are 20-to 22-nucleotide noncoding RNA molecules that have emerged as key players in controlling NSC self-renewal and differentiation (11,57). Aberrant expression of miRNAs, such as miR-21, miR-124, and miR-137, is linked to glioma formation (49). miR-199b-5p and miR-34a impair cancer stem-like cells through the negative regulation of several components of the Notch pathway in brain tumors (18,21). The Notch pathway is an evolutionarily conserved signaling pathway that plays an important role in neurogenesis (3, 10, 23). Upon bindi...

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“…Continuing the stem cell theme, Godlewski et al 20 review the role of miRs in glioblastoma, a tumour thought to be derived from neural stem cells. Indeed, the miR profiles of neural stem cells and glioblastoma cells are strikingly similar.…”

mentioning

confidence: 99%