MBRS-41. DIFFERENTIAL microRNA EXPRESSION IN THE MOLECULAR SUBGROUPS OF MEDULLOBLASTOMAS: ROLE IN TUMOR BIOLOGY AND CLINICAL CHARACTERISTICS

Abstract Over 250 medulloblastoma tumors tissues from an Indian cohort have been molecularly classified using the microRNA based real time RT-PCR assay and correlated with clinical characteristics. The Indian cohort continues to show three distinct features viz. higher incidence of the WNT tumors particularly in the adult patients, higher male:female (9:1) ratio of Group 4 tumors and their lower incidence in adults. At the functional level, we have studied the effect of expression of several miRNAs differentially expressed in the medulloblastoma subgroups. The miRNA encoding genes were expressed in multiple medulloblastoma cell lines using inducible lentiviral vectors. MiR-193a expression was found to inhibit anchorage-independent growth and tumorigenicity of medulloblastoma cell lines. MiR-224 expression was found to increase radiation sensitivity of both medulloblastoma and glioblastoma cells and was found to down-regulate Apoptosis Inhibitor 5 gene. MiR-148a expression was found to inhibit tumorigenic and invasion potential of multiple medulloblastoma cells lines by targeting NRP1. MiR-30a and miR-206 are downregulated in all medulloblastoma subgroups as compared to normal brain tissues. MiR-30a was found to inhibit autophagy by targeting Beclin1 in medulloblastoma cells while miR-206 targets OTX2. Studies on two microRNAs miR-592 and miR-204, differentially expressed in the Group 3/Group 4 medulloblastomas will be presented.