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Molecular and functional characterization of USP2 in pediatric Medulloblastomas of Groups 3 and 4

Grant number: 22/15919-9
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): May 01, 2023
Effective date (End): April 30, 2024
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Carlos Alberto Scrideli
Grantee:Jonas José da Silva
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Medulloblastomas (MBs) of Groups 3 and 4 are malignant tumors of embryonic origin. Unfortunately, to date, these molecular groups are scarce in the characterization of new biomarkers for therapeutic purposes, which reflects a worse prognosis of the disease and an increase in relapses. In light of the above, we draw attention to the USP2 gene, a putative effector of cross-talks between the nuclear factor kappa B (NF-KB) pathway with crucial genes of the cellular immune response. USP2 is a biomarker of worse prognosis and a promising therapeutic target in several cancers. To our surprise, the role of USP2 in the carcinogenesis of Group 3 and 4 MBs has not been investigated. Therefore, initially, through in silico analysis, we identified the overexpression of USP2. This expression profile was associated with metastasis and worse survival in patients diagnosed with MBs in Groups 3 and 4. Therefore, it becomes necessary to evaluate the biological functionality of the USP2 knockdown in Groups 3 and 4 MBs through representative in vitro functional assays combined with cisplatin treatment. Furthermore, we aim to identify the respective USP2 cross-talk targets in the cell, as mentioned earlier, signaling pathways, by performing transcriptomic data integration and, later, validating them by qRT-PCR and WB. Finally, this project could elucidate a better understanding of the biogenesis of Groups 3 and 4 MBs by evaluating USP2 as a new therapeutic target perspective. On the tangents of the MB study, a pioneering proposal would bring gains to the advancement of scientific and technological development.

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