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RNA-Binding Protein Musashi1 Is a Central Regulator of Adhesion Pathways in Glioblastoma
- Source :
- Molecular and Cellular Biology. 35:2965-2978
- Publication Year :
- 2015
- Publisher :
- Informa UK Limited, 2015.
-
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.
- Subjects :
- Cell Survival
Nerve Tissue Proteins
RNA-binding protein
Biology
Cell Movement
RNA interference
Cell Line, Tumor
Cell Adhesion
Humans
Neoplasm Invasiveness
RNA, Small Interfering
Cell adhesion
3' Untranslated Regions
Molecular Biology
Cell Proliferation
Genetics
Binding Sites
Base Sequence
Sequence Analysis, RNA
Three prime untranslated region
Alternative splicing
RNA-Binding Proteins
RNA
Articles
Cell Biology
Cell biology
Alternative Splicing
RNA splicing
RNA Interference
Glioblastoma
ICLIP
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....2faa8a53565cde21286b41898581fd2b
- Full Text :
- https://doi.org/10.1128/mcb.00410-15