Format

Send to

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

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

Author information

1
Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California, USA.
2
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
3
University Medical Center, Department of Children's Hospital, Halle (Saale), Germany.
4
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
5
School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil Department of Pathology, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, Georgia, USA.
6
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom.
7
Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
8
Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, California, USA andrewds@usc.edu penalva@uthscsa.edu.
9
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA andrewds@usc.edu penalva@uthscsa.edu.

Abstract

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.

PMID:
26100017
PMCID:
PMC4525321
DOI:
10.1128/MCB.00410-15
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center