Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma

Abstract

Despite recent advances in treatment medulloblastoma continues to remain a vexing problem. Recently increased expression of cyclin dependent kinase 6 (CDK6) was identified as an adverse prognostic marker in medulloblastoma. Genomic amplification accounts for some, but not all of the CDK6 over-expression. We hypothesized that CDK6 expression is also regulated by microRNAs in medulloblastoma. We identified putative miR sites in the CDK6 including microRNA 124a, a brain enriched microRNA. Expression of miR 124a was significantly decreased in medulloblastoma cells compared to normal adult cerebellum. Functional association between miR 124a and CDK6 in medulloblastoma was established using luciferase assays. Additionally, re-expression of miR 124a in medulloblastoma cells decreased expression of CDK6 protein. Transfection of miR 124 significantly decreases medulloblastoma cell growth but does not alter apoptosis. Furthermore, in patient samples expression of miR 124a is significantly decreased. Our data strongly indicate that CDK6 is regulated by microRNA 124 in medulloblastoma and that miR 124 modulates medulloblastoma cell growth.