gms | German Medical Science

Objective: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by translational inhibition or cleavage of target mRNAs. We investigated the potential role of altered miRNA expression in the pathogenesis of medulloblastoma, the most common malignant brain tumor in children. Among the set of differentially expressed miRNAs, we focused on miR-134 as an interesting candidate that has been reported to be involved in neural precursor cell differentiation as well as neuronal maturation and function.

Method: Microarray-based miRNA expression profiling was used to determine the expression levels of 380 miRNAs in 10 medulloblastomas from Ptch1^+/- mice in relation to immature (postnatal day 5-9) and adult normal murine cerebellar tissue.

Results: MicroRNA-134 was significantly down-regulated in murine medulloblastomas as compared to immature cerebellar tissue. Expression analysis of miR-134 in human medulloblastomas revealed significantly lower expression levels in both classic and desmoplastic medulloblastomas when compared to normal human cerebellar tissue. Functional analyses of medulloblastoma cell lines revealed significantly reduced proliferation after transfection of miR-134 precursor molecules. Using miR-134 programmed RNA immunoprecipation we identified NMYC as a potential target regulated by miR-134. Direct regulation of NMYC by miR-134 was confirmed in 3’-UTR luciferase assays.

Conclusions: In summary, our results indicate that down-regulation of miR-134 may contribute to medulloblastoma pathogenesis by facilitating NMYC-dependent growth promotion.