Identification and Functional Characterization of Novel MYC-Regulated Long Noncoding RNAs in Group 3 Medulloblastoma

Abstract

The impact of protein-coding genes on cancer onset and progression is a well-established paradigm in molecular oncology. Nevertheless, unveiling the contribution of the noncoding genes—including long noncoding RNAs (lncRNAs)—to tumorigenesis represents a great challenge for personalized medicine, since they (i) constitute the majority of the human genome, (ii) are essential and flexible regulators of gene expression and (iii) present all types of genomic alterations described for protein-coding genes. LncRNAs have been increasingly associated with cancer, their highly tissue- and cancer type-specific expression making them attractive candidates as both biomarkers and therapeutic targets. Medulloblastoma is one of the most common malignant pediatric brain tumors. Group 3 is the most aggressive subgroup, showing the highest rate of metastasis at diagnosis. Transcriptomics and reverse genetics approaches were combined to identify lncRNAs implicated in Group 3 Medulloblastoma biology. Here we present the first collection of lncRNAs dependent on the activity of the MYC oncogene, the major driver gene of Group 3 Medulloblastoma. We assessed the expression profile of selected lncRNAs in Group 3 primary tumors and functionally characterized these species. Overall, our data demonstrate the direct involvement of three lncRNAs in Medulloblastoma cancer cell phenotypes.