TY - JOUR
T1 - High-throughput microRNA profiling of pediatric high-grade gliomas
AU - Miele, Evelina
AU - Buttarelli, Francesca Romana
AU - Arcella, Antonella
AU - Begalli, Federica
AU - Garg, Neha
AU - Silvano, Marianna
AU - Po, Agnese
AU - Baldi, Caterina
AU - Carissimo, Giuseppe
AU - Antonelli, Manila
AU - Spinelli, Gian Paolo
AU - Capalbo, Carlo
AU - Donofrio, Vittoria
AU - Morra, Isabella
AU - Nozza, Paolo
AU - Gulino, Alberto
AU - Giangaspero, Felice
AU - Ferretti, Elisabetta
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - cancer
KW - expression profiling
KW - microRNA
KW - pediatric gliomas
UR - http://www.scopus.com/inward/record.url?scp=84893122766&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893122766&partnerID=8YFLogxK
U2 - 10.1093/neuonc/not215
DO - 10.1093/neuonc/not215
M3 - Article
C2 - 24305714
AN - SCOPUS:84893122766
VL - 16
SP - 228
EP - 240
JO - Neuro-Oncology
JF - Neuro-Oncology
SN - 1522-8517
IS - 2
ER -