Musashi1 Contribution to Glioblastoma Development via Regulation of a Network of DNA Replication, Cell Cycle and Division Genes

Cancers

Mitzli Velasco¹  LuizO. F. Penalva¹  Denise Grieshober¹  Mirella Baroni¹  Talia DeLambre¹  Mei Qiao¹  Caihong Yi¹  Xiufen Lei¹  Adam Kosti¹  PatriciaR. Araujo¹  SuzanneS. Burns¹  Saket Choudhary²  MiYoung Son³  Paul Hasty³  MarcoA. R. Ferreira⁴  Michelina Plateroti⁵ 

[1] Children’s Cancer Research Institute, UT Health San Antonio, San Antonio, TX 78229, USA;Computational Biology and Bioinformatics, University of Southern California, Los Angeles, CA 90089, USA;Department of Molecular Medicine, Sam and Ann Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX 78229, USA;Department of Statistics, Virginia Tech, Blacksburg, VA 24060, USA;Team: Development, Cancer and Stem Cells, Université de Strasbourg, Inserm, IRFAC/UMR-S1113, FMTS, 67200 Strasbourg, France;

关键词: glioblastoma;    Musashi1;    cell cycle;    DNA replication;    cell division;    E2F2;   

DOI  :  10.3390/cancers13071494

来源: DOAJ

【 摘 要 】

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 self-renewal 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.

【 授权许可】

Unknown