Details

Autor(en) / Beteiligte

• Chagas, Pablo Shimaoka
• Veronez, Luciana Chain
• de Sousa, Graziella Ribeiro
• Cruzeiro, Gustavo Alencastro Veiga
• Corrêa, Carolina Alves Pereira
• Saggioro, Fabiano Pinto
• de Paula Queiroz, Rosane Gomes
• Marie, Suely Kazue Nagahashi
• Brandalise, Silvia Regina
• Cardinalli, Izilda Aparecida
• Yunes, José Andres
• Júnior, Carlos Gilberto Carlotti
• Machado, Hélio Rubens
• Santos, Marcelo Volpon
• Scrideli, Carlos Alberto
• Tone, Luiz Gonzaga
• Valera, Elvis Terci

Titel

Musashi-1 regulates cell cycle and confers resistance to cisplatin treatment in Group 3/4 medulloblastomas cells

Ist Teil von

• Human cell : official journal of Human Cell Research Society, 2023-11, Vol.36 (6), p.2129-2139

Ort / Verlag

Singapore: Springer Nature Singapore

Erscheinungsjahr

2023

Quelle

SpringerLink

Beschreibungen/Notizen

• Groups (Grp) 3 and 4 are aggressive molecular subgroups of medulloblastoma (MB), with high rates of leptomeningeal dissemination. To date, there is still a paucity of biomarkers for these subtypes of MBs. In this study, we investigated the clinical significance and biological functions of Musashi-1 ( MSI1) in Grp3 and Grp4-MBs. First, we assessed the expression profile of MSI1 in 59 primary MB samples (15-WNT, 18-SHH, 9-Grp3, and 17-Grp4 subgroups) by qRT-PCR. MSI1 mRNA expression levels were also validated in an additional public dataset of MBs (GSE85217). The ROC curve was used to validate the diagnostic standards of MSI1 expression. Next, the potential correlated cell-cycle genes were measured by RNA-Seq. Cell cycle, cell viability, and apoptosis were evaluated in a Grp3/Grp4 MB cell line after knockdown of MSI1 and cisplatin treatment. We identified an overexpression of MSI1 with a high accuracy to discriminate Grp3/Grp4-MBs from non-Grp3/Grp4-MBs. We identified that MSI1 knockdown not only triggered transcriptional changes in the cell-cycle pathway, but also affected G2/M phase in vitro, supporting the role of knockdown of MSI1 in cell-cycle arrest. Finally, MSI1 knockdown decreased cell viability and sensitized D283-Med cells to cisplatin treatment by enhancing cell apoptosis. Based on these findings, we suggest that MSI1 modulates cell-cycle progression and may play a role as biomarker for Grp3/Grp4-MBs. In addition, MSI1 knockdown combined with cisplatin may offer a potential strategy to be further explored in Grp3/Grp4-MBs.