High-throughput microRNA profiling of pediatric high-grade gliomas

Evelina Miele, Francesca Romana Buttarelli, Antonella Arcella, Federica Begalli, Neha Garg, Marianna Silvano, Agnese Po, Caterina Baldi, Giuseppe Carissimo, Manila Antonelli, Gian Paolo Spinelli, Carlo Capalbo, Vittoria Donofrio, Isabella Morra, Paolo Nozza, Alberto Gulino, Felice Giangaspero, Elisabetta Ferretti

Research output: Contribution to journalArticle

Abstract

BackgroundHigh-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.MethodsWe 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.ConclusionsOur results suggest that microRNA profiling represents a tool to distinguishing pediatric from adult HGG and that miR-17-92 cluster sustains pHGG.

Original languageEnglish
Pages (from-to)228-240
Number of pages13
JournalNeuro-Oncology
Volume16
Issue number2
DOIs
Publication statusPublished - Jan 2014

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Keywords

  • cancer
  • expression profiling
  • microRNA
  • pediatric gliomas

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Miele, E., Buttarelli, F. R., Arcella, A., Begalli, F., Garg, N., Silvano, M., Po, A., Baldi, C., Carissimo, G., Antonelli, M., Spinelli, G. P., Capalbo, C., Donofrio, V., Morra, I., Nozza, P., Gulino, A., Giangaspero, F., & Ferretti, E. (2014). High-throughput microRNA profiling of pediatric high-grade gliomas. Neuro-Oncology, 16(2), 228-240. https://doi.org/10.1093/neuonc/not215