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

Pablo Shimaoka Chagas1, Luciana Chain Veronez2, Graziella Ribeiro de Sousa3

  • 1Department of Genetics, Ribeirão Preto Medical School-University of São Paulo, Bandeirantes Avenue, 3900, Ribeirão Preto, São Paulo, 14048-900, Brazil. pablochagas@usp.br.

Human Cell
|July 17, 2023
PubMed

Insights

Musashi-1 (MSI1) is overexpressed in aggressive medulloblastoma (MB) Groups 3 and 4, acting as a potential biomarker. MSI1 knockdown halts cell-cycle progression and sensitizes MB cells to cisplatin, suggesting a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Medulloblastoma (MB) Groups 3 and 4 are aggressive subtypes with high metastatic potential.
  • Biomarkers for these MB subgroups are currently limited.
  • Musashi-1 (MSI1) is a potential target for investigation in these aggressive MBs.

Purpose of the Study:

  • To investigate the clinical significance and biological functions of MSI1 in Group 3 and Group 4 medulloblastoma.
  • To evaluate MSI1 as a potential biomarker for discriminating between MB subgroups.
  • To explore the therapeutic potential of targeting MSI1 in combination with cisplatin.

Main Methods:

  • Quantitative reverse transcription PCR (qRT-PCR) to assess MSI1 mRNA expression in primary MB samples.
  • RNA sequencing (RNA-Seq) to identify cell-cycle genes correlated with MSI1 expression.
  • In vitro studies involving MSI1 knockdown in a Group 3/4 MB cell line, followed by assessments of cell cycle, viability, and apoptosis.
  • Analysis of MSI1 expression using ROC curves for diagnostic accuracy.

Main Results:

  • MSI1 was found to be overexpressed in Group 3 and Group 4 MBs with high diagnostic accuracy.
  • MSI1 knockdown led to transcriptional changes in cell-cycle pathways and induced G2/M phase arrest.
  • Knockdown of MSI1 reduced cell viability and enhanced apoptosis in MB cells.
  • MSI1 knockdown sensitized D283-Med cells to cisplatin treatment.

Conclusions:

  • MSI1 plays a role in modulating cell-cycle progression in medulloblastoma.
  • MSI1 is a promising biomarker for identifying aggressive Group 3 and Group 4 medulloblastoma subtypes.
  • Combining MSI1 knockdown with cisplatin presents a potential therapeutic strategy for Group 3/4 MBs.
Keywords:
Grp3-MBGrp4-MBsMedulloblastomaMusashi-1RNA-binding protein

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