Birks DK, Barton VN, Donson AM, et al. Survey of MicroRNA expression in pediatric brain tumors

Department of Neurosurgery, Anschutz Medical Campus, University of Colorado at Denver, Aurora, Colorado 80045, USA.
Pediatric Blood & Cancer (Impact Factor: 2.39). 02/2011; 56(2):211-6. DOI: 10.1002/pbc.22723
Source: PubMed


A better understanding of pediatric brain tumor biology is needed to assist in the development of less toxic therapies and to provide better markers for disease stratification. MicroRNAs (miRNA) may play a significant role in brain tumor biology. The present study provides an initial survey of miRNA expression in pediatric central nervous system (CNS) malignancies including atypical teratoid/rhabdoid tumor, ependymoma, glioblastoma, medulloblastoma, and pilocytic astrocytoma.
MicroRNA expression in pediatric brain tumors and normal tissue controls was examined by microarray. Three aberrantly expressed miRNAs were further studied in a larger cohort by quantitative real-time PCR (qRT-PCR).
MicroRNA-129, miR-142-5p, and miR-25 were differentially expressed in every pediatric brain tumor type compared to normal tissue controls as measured by microarray. When further examined by qRT-PCR, these miRNAs demonstrated differential expression that significantly correlated with the microarray findings. Distinctive miRNA expression profiles were also observed in the different pediatric brain tumor types.
MicroRNAs are differentially expressed between pediatric CNS neoplasms and normal tissue suggesting that they may play a significant role in oncogenesis. A greater understanding of aberrant miRNA expression in pediatric brain tumors may aid in the development of novel therapies. The characterization of tumor-specific miRNA signatures may aid in the discovery of biomarkers with diagnostic or prognostic utility.

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    • "Pediatric brain tumors Birks et al. (2011) "
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    ABSTRACT: A better understanding of pediatric tumor biology is needed to allow the development of less toxic and more efficient therapies, as well as to provide novel reliable biomarkers for diagnosis and risk stratification. The emerging role of microRNAs in controlling key pathways implicated in tumorigenesis makes their use in diagnostics a powerful novel tool for the early detection, risk assessment and prognosis, as well as for the development of innovative anticancer therapies. This perspective would be more urgent for the clinical management of pediatric cancer. In this review, we focus on the involvement of microRNAs in the biology of the main childhood tumors, describe their clinical significance and discuss their potential use as novel therapeutic tools and targets. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Full-text · Article · Mar 2015 · Acta Histochemica
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    • "Alterations in miRNA expression levels are associated with a number of neural diseases [12] [13] [14] [15] and brain tumors [16] [17] [18]. Recently, specific miRNA expression profiles have been identified in GBMs [17] [18], but there are only miRNA expression profiles in pediatric glioblastoma multiforme 232 Am J Cancer Res 2015;5(1):231-242 limited data on the role of miRNA in pediatric GBM [19] [20]. miR-21 is an important oncogenic miRNA that promotes cell invasion, by regulating multiple genes, including PTEN, RECK and MARCKS, in several types of cancers, such as glioma, ovarian epithelial carcinoma and prostate cancer [21] [22] [23]. "
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    ABSTRACT: Various signal transduction pathways seem to be involved in chemoresistance mechanism of glioblastomas (GBMs). miR-21 is an important oncogenic miRNA which modulates drug resistance of tumor cells. We analyzed the expression of 5 miRNAs, previously found to be dysregulated in high grade gliomas, in 9 pediatric (pGBM) and in 5 adult (aGBM) GBMs. miR-21 was over-expressed, with a significant difference between pGBMs and aGBMs represented by a 4 times lower degree of expression in the pediatric compared to the adult series (p = 0.001). Doxorubicin (Dox) seems to be an effective anti-glioma agent with high antitumor activity also against glioblastoma stem cells. We therefore evaluated the chemosensitivity to Dox in 3 GBM cell lines (A172, U87MG and T98G). Dox had a cytotoxic effect after 48 h of treatment in A172 and U87MG, while T98G cells were resistant. TUNEL assay verified that Dox induced apoptosis in A172 and U87MG but not in T98G. miR-21 showed a low basal expression in treated cells and was over-expressed in untreated cells. To validate the possible association of miR-21 with drug resistance of T98G cells, we transfected anti-miR-21 inhibitor into the cells. The expression level of miR-21 was significantly lower in T98G transfected cells (than in the parental control cells). Transfected cells showed a high apoptotic rate compared to control after Dox treatment by TUNEL assay, suggesting that combined Dox and miR-21 inhibitor therapy can sensitize GBM resistant cells to anthracyclines by enhancing apoptosis.
    Full-text · Article · Jan 2015 · American Journal of Cancer Research
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    • "Recently, Birks et al analyzed miRNA profiles in 24 pediatric CNS tumors including 4 HGG WHO grade IV. Our study includes a wider series of pHGGs, confirming a deregulation of miRNA-129, miR-142-5p, and miR-25 that suggests their general role in all pediatric brain tumorigeneses.39 By extending these findings, we were able to describe specifically deregulated miRNAs in pHGG that highlighted the upregulation of miR-17-92 cluster. "
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    ABSTRACT: Background High-grade gliomas (HGGs) account for 15% of all pediatric brain tumors and are a leading cause of cancer-related mortality and morbidity. Pediatric HGGs (pHGGs) are histologically indistinguishable from their counterpart in adulthood. However, recent investigations indicate that differences occur at the molecular level, thus suggesting that the molecular path to gliomagenesis in childhood is distinct from that of adults. MicroRNAs (miRNAs) have been identified as key molecules in gene expression regulation, both in development and in cancer. miRNAs have been investigated in adult high-grade gliomas (aHGGs), but scant information is available for pHGGs.Methods We explored the differences in microRNAs between pHGG and aHGG, in both fresh-frozen and paraffin-embedded tissue, by high-throughput miRNA profiling. We also evaluated the biological effects of miR-17-92 cluster silencing on a pHGG cell line.ResultsComparison of miRNA expression patterns in formalin versus frozen specimens resulted in high correlation between both types of samples. The analysis of miRNA profiling revealed a specific microRNA pattern in pHGG with an overexpression and a proliferative role of the miR-17-92 cluster. Moreover, we highlighted a possible quenching function of miR-17-92 cluster on its target gene PTEN, together with an activation of tumorigenic signaling such as sonic hedgehog in pHGG.Conclusions Our results suggest that microRNA profiling represents a tool to distinguishing pediatric from adult HGG and that miR-17-92 cluster sustains pHGG.
    Full-text · Article · Dec 2013 · Neuro-Oncology
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