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<p>Medulloblastoma (MB), the most common malignant pediatric brain tumor, is classified into four molecular groups: WNT, SHH, G3, and G4. G3 and G4 MBs are characterized by poor prognosis and high metastatic potential. Although USP2 (ubiquitin-specific peptidase 2) has been described as a prognostic biomarker and a promising therapeutic target in several cancer types, its role in the pathogenesis of G3 and G4 MBs remains unexplored. In this study, USP2 expression was investigated through in silico analyses, public datasets (GSE85217), and tumor samples from 54 pediatric MB patients. In addition, the effects of USP2 inhibition were evaluated in two G3/G4 MB cell lines (D283 Med and USP-13) using ML364, a selective USP2 inhibitor. USP2 was overexpressed in G3 and G4 MBs and was associated with metastasis and unfavorable clinical outcomes. Furthermore, ML364 treatment reduced USP2 protein expression level, as well as cell viability, migration, invasion, and colony-forming capacity in both cell lines. These findings indicate that USP2 is upregulated in pediatric G3 and G4 MBs and support its potential role as a biomarker of poor prognosis and a therapeutic target in these molecular subgroups.</p>

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Therapeutic Potential of Targeting USP2 in Pediatric Group 3 and 4 Medulloblastomas: Insights from In Silico, Ex Vivo, and In Vitro Studies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月9日

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  • Jonas José da Silva,
  • Manuela Eduarda de França,
  • Alcides Euzebio Tavares Xavier,
  • Mariane Minussi Baptistella,
  • Eduardo Afonso da Silva Pereira,
  • Marina Ferreira Cândido,
  • Luis Fernando Peinado Nagano,
  • Jéssica Oliveira de Santis,
  • Rosane Gomes de Paula Queiroz,
  • Silvia Regina Brandalise,
  • José Andres Yunes,
  • Luiz Gonzaga Tone,
  • Elvis Terci Valera,
  • Pablo Shimaoka Chagas,
  • Carlos Alberto Scrideli

摘要

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is classified into four molecular groups: WNT, SHH, G3, and G4. G3 and G4 MBs are characterized by poor prognosis and high metastatic potential. Although USP2 (ubiquitin-specific peptidase 2) has been described as a prognostic biomarker and a promising therapeutic target in several cancer types, its role in the pathogenesis of G3 and G4 MBs remains unexplored. In this study, USP2 expression was investigated through in silico analyses, public datasets (GSE85217), and tumor samples from 54 pediatric MB patients. In addition, the effects of USP2 inhibition were evaluated in two G3/G4 MB cell lines (D283 Med and USP-13) using ML364, a selective USP2 inhibitor. USP2 was overexpressed in G3 and G4 MBs and was associated with metastasis and unfavorable clinical outcomes. Furthermore, ML364 treatment reduced USP2 protein expression level, as well as cell viability, migration, invasion, and colony-forming capacity in both cell lines. These findings indicate that USP2 is upregulated in pediatric G3 and G4 MBs and support its potential role as a biomarker of poor prognosis and a therapeutic target in these molecular subgroups.