Musashi-1 gene in medulloblastoma group 3 and 4

• Grant number: 17/26160-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2020
• End date: December 31, 2021
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Luiz Gonzaga Tone
• Grantee: Pablo Shimaoka Chagas
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/20341-0 - Interactions between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on pediatric malignancies, AP.TEM

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DAS CHAGAS, PABLO FERREIRA; DE SOUSA, GRAZIELLA RIBEIRO; VERONEZ, LUCIANA CHAIN; MARTINS-DA-SILVA, ANDREA; CORREA, CAROLINA ALVES PEREIRA; CRUZEIRO, GUSTAVO ALENCASTRO VEIGA; NAGANO, LUIS FERNANDO PEINADO; QUEIROZ, ROSANE GOMES DE PAULA; MARIE, SUELY KAZUE NAGAHASHI; BRANDALISE, SILVIA REGINA; et al. Identification of ITPR1 as a Hub Gene of Group 3 Medulloblastoma and Coregulated Genes with Potential Prognostic Values. JOURNAL OF MOLECULAR NEUROSCIENCE, NOV 2021. (17/26160-5, 14/20341-0)

VERONEZ, LUCIANA C.; DAS CHAGAS, PABLO F.; CORREA, CAROLINA A. P.; BARONI, MIRELLA; DA SILVA, KETERYNE R.; NAGANO, LUIS F.; BORGES, KLEITON S.; QUEIROZ, ROSANE G. P.; TONE, LUIZ G.; SCRIDELI, CARLOS A.. MSI2 expression in adrenocortical carcinoma: Association with unfavorable prognosis and correlation with steroid and immune-related pathways. Journal of Cellular Biochemistry, v. 122, n. 12, SEP 2021. (18/04477-0, 14/20341-0, 17/26160-5)