Musashi1 contribution to glioblastoma development via regulation of a network of dna replication, cell cycle and division genes

Mirella Baroni, Caihong Yi, Saket Choudhary, Xiufen Lei, Adam Kosti, Denise Grieshober, Mitzli Velasco, Mei Qiao, Suzanne S. Burns, Patricia R. Araujo, Talia Delambre, Mi Young Son, Michelina Plateroti, Marco A.R. Ferreira, Paul Hasty, Luiz O.F. Penalva

Research output: Contribution to journalArticlepeer-review

Abstract

RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in their levels are often observed in tumors with numerous oncogenic RBPs identified in recent years. Musashi1 (Msi1) is an RBP and stem cell gene that controls the balance between selfrenewal and differentiation. High Msi1 levels have been observed in multiple tumors including glioblastoma and are often associated with poor patient outcomes and tumor growth. A comprehensive genomic analysis identified a network of cell cycle/division and DNA replication genes and established these processes as Msi1’s core regulatory functions in glioblastoma. Msi1 controls this gene network via two mechanisms: direct interaction and indirect regulation mediated by the transcription factors E2F2 and E2F8. Moreover, glioblastoma lines with Msi1 knockout (KO) displayed increased sensitivity to cell cycle and DNA replication inhibitors. Our results suggest that a drug combination strategy (Msi1 + cell cycle/DNA replication inhibitors) could be a viable route to treat glioblastoma.

Original languageEnglish (US)
Article number1494
JournalCancers
Volume13
Issue number7
DOIs
StatePublished - Apr 1 2021

Keywords

  • Cell cycle
  • Cell division
  • DNA replication
  • E2F2
  • E2F8
  • Glioblastoma
  • Musashi1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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