High-throughput microRNA profiling of pediatric high-grade gliomas

Background.High-gradegliomas(HGGs)accountfor15%ofallpediatricbraintumorsandarealeadingcauseofcancer-relatedmortality and morbidity. Pediatric HGGs (pHGGs) are histologically indistinguishable from theircounterpart in adulthood. However, recent investigations indicate that differences occurat 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. Results.ComparisonofmiRNAexpressionpatternsinformalinversusfrozenspecimensresultedinhighcorrelationbetweenbothtypesof 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.OurresultssuggestthatmicroRNAprofilingrepresentsatooltodistinguishingpediatricfromadultHGGandthatmiR-17-92 cluster sustains pHGG.