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Differential microRNA expression in molecular subgroups of medulloblastomas: role in pathogenesis, diagnosis and therapeutic potential


We have carried out microRNA profiling of medulloblastomas in parallel with genome-wide expression profiling of protein-coding genes that identified differential miRNA expression in the four molecular subgroups of medulloblastomas, with the most distinctive miRNA profile of WNT subgroup tumours. Differential expression of eleven miRNAs across the four subgroups was validated by real-time RT-PCR in a set of 103 medulloblastomas. The WNT subgroup tumors showed significant (p < 0.0001) over-expression of miR-193a-3p, miR-224, miR-148a, miR-23b, miR-365, and miR-10b as compared to all other subgroup medulloblastomas. A real-time RT-PCR assay evaluating the expression profile of 12 protein-coding genes and 9 miRNAs was developed for molecular classification of medulloblastomas with an overall accuracy of 97%. The assay is rapid, simple and inexpensive. It is particularly useful for the classification of FFPE tumor tissues, wherein the expression profile of protein-coding genes is often less reliable due to RNA fragmentation. Further, Non-WNT, non-SHH medulloblastomas over-expressing miR-182 or under-expressing miR-592 were found to have significantly inferior survival rates indicating utility of these two miRNAs as markers for risk stratification of medulloblastomas. We have been studying functional role of several miRNAs in medulloblastoma biology. In particular, miR-193a, an miRNA up-regulated specifically in WNT subgroup medulloblastoma was found to inhibit proliferation, anchorage-independent growth and inhibit tumourigenicity of medulloblastoma cells indicating its therapeutic potential.

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