RNA-Binding Protein Musashi1 Is a Central Regulator of Adhesion Pathways in Glioblastoma

Mol Cell Biol. 2015 Sep 1;35(17):2965-78. doi: 10.1128/MCB.00410-15. Epub 2015 Jun 22.


The conserved RNA-binding protein Musashi1 (MSI1) has emerged as a key oncogenic factor in numerous solid tumors, including glioblastoma. However, its mechanism of action has not yet been established comprehensively. To identify its target genes comprehensively and determine the main routes by which it influences glioblastoma phenotypes, we conducted individual-nucleotide resolution cross-linking and immunoprecipitation (iCLIP) experiments. We confirmed that MSI1 has a preference for UAG sequences contained in a particular structural context, especially in 3' untranslated regions. Although numerous binding sites were also identified in intronic sequences, our RNA transcriptome sequencing analysis does not favor the idea that MSI1 is a major regulator of splicing in glioblastoma cells. MSI1 target mRNAs encode proteins that function in multiple pathways of cell proliferation and cell adhesion. Since these associations indicate potentially new roles for MSI1, we investigated its impact on glioblastoma cell adhesion, morphology, migration, and invasion. These processes are known to underpin the spread and relapse of glioblastoma, in contrast to other tumors where metastasis is the main driver of recurrence and progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alternative Splicing / genetics
  • Base Sequence
  • Binding Sites / genetics
  • Cell Adhesion / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • RNA Interference
  • RNA, Small Interfering
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics*
  • Sequence Analysis, RNA


  • 3' Untranslated Regions
  • MSI1 protein, human
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins

Associated data

  • GEO/GSE68800