Musashi-1 gene in medulloblastoma group 3 and 4

Abstract

Medulloblastoma (MB) is the malignant neoplasm of the central nervous system most commonly diagnosed in pediatric patients. MB is assigned into 4 molecular subgroups: WNT, SHH, MB of Group 3 and Group 4. MB Group 3 and 4 are molecularly poorly understood and presents a high rate of metastasis and relapse. Trought in silico analysis we showed that in Group 3 and 4 MB, there is an overexpression of Musashi-1 (MSI1) when compared to others molecular subgroups. MSI1 is an RNA binding protein that is strongly associated with poor prognosis, suggesting that this molecule has a potential role in the progression of cancer. Therefore, this project aims to evaluate the role of MSI1 in MB tumorigenesis in these molecular subgroups. We evaluated the expression of MSI1 in 64 MBs from HC-FMRP and Boldrini Institute patients and found concordance with in silico analysis. Further, will be performed the MSI1 Knockdown trought RNAi technology in vitro of MB Group 3 and 4 to assess chemosensitivity to agents Lomustine and Cisplatin trought proliferation, migration and apoptosis assays. Further, will be assessed the impact of MSI1 in Notch pathway, which have an important role in cerebellar development and homeostasis. Finally, this project will not only elucidate the biology of MB Group 3 and Group 4 trought assessment MSI1 as a potential therapeutic target, and the impact of this gene in Notch signaling pathway. (AU)