Speaker
Description
Medulloblastoma (MB) is the most common pediatric brain tumor, and current therapies fail in about 30% of cases due to fatal recurrences. To address effective therapeutic strategies against MB, a better modeling of the tumor microenvironment is needed.
Here, we firstly developed an orthotopic xenotransplantation model of human MB in wild-type mouse embryos, which recapitulates the MB microenvironment, including angiogenesis, cancer stem cell (CSC) niche and neuro-immune crosstalk, within a developmental context.
We then exploited the embryonic xenotransplantation model of MB to test the therapeutic potential of a combination of eleven microRNAs (miRNAs), which we previously showed to rescue impaired neurogenesis of miRNA-depleted neural stem cells. We demonstrate that the eleven miRNAs are downregulated across various human MB subtypes. Upon rescue of expression of the eleven miRNAs in human MB cells in vitro and in vivo, we show by multi-omics analyses that the pool of eleven miRNA exerts an anticancer activity by modulating key genes and pathways involved in proliferation, differentiation and migration.
This study demonstrates that our model recapitulates human MB development and microenvironment and is suitable for testing RNA-based therapies. Finally, our results emphasize the therapeutic potential of the synergistic action of multiple miRNAs as anticancer strategy for MB, and possibly other tumors.
| Author(s) | Letizia La Rosa*1, Carlotta Spattini*1-2, Roberta Pelizzoli1, Rui Pereira1-3, Davide De Pietri Tonelli1 |
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| Affiliation(s) | "1 Neurobiology of miRNA lab, Istituto Italiano di Tecnologia, via Morego 30, 16163 Genoa (Italy) 2 The Open University Affiliated Research Centre, Fondazione Istituto Italiano di Tecnologia, Genova, Italy 3 i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto 4200-180 (Portugal) Presenting Author: Letizia La Rosa" |
