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Sci Rep. 2017 Aug 18;7(1):8710. doi: 10.1038/s41598-017-09504-7.

Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3.

Chen HY1, Lin LT2,3,4, Wang ML2,5, Laurent B6, Hsu CH6,7, Pan CM5,8, Jiang WR3, Chen PY9, Ma HI10, Chen YW1,11, Huang PI1,11, Chiou A12, Chiou SH13,14,15,16,17.

Author information

1
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
2
Stem Cell Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
3
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
4
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
5
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
6
Boston Children Hospital and Harvard Medical School, Boston, MA, USA.
7
Program in Epigenetic and Molecular Cell Biology, School of Medicine and Public Health, Zhejiang University, Hangzhou, China.
8
Center for Cell Therapy, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
9
Institute of Biomedical Engineering, National Chiao-Tung University, Hsinchu, Taiwan.
10
Department of Neurological Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.
11
Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.
12
Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan.
13
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. shchiou@vghtpe.gov.tw.
14
Stem Cell Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. shchiou@vghtpe.gov.tw.
15
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. shchiou@vghtpe.gov.tw.
16
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan. shchiou@vghtpe.gov.tw.
17
Genomic Research Center, Academia Sinica, Taipei, Taiwan. shchiou@vghtpe.gov.tw.

Abstract

The RNA-binding protein Musashi-1 (MSI1) exerts essential roles in multiple cellular functions, such as maintenance of self-renewal and pluripotency of stem cells. MSI1 overexpression has been observed in several tumor tissues, including glioblastoma (GBM), and is considered as a well-established marker for tumor metastasis and recurrence. However, the molecular mechanisms by which MSI1 regulates cell migration are still undetermined. Here we reported that MSI1 alters cell morphology, promotes cell migration, and increases viscoelasticity of GBM cells. We also found that MSI1 directly binds to the 3'UTR of Tensin 3 (TNS3) mRNA, a negative regulator of cell migration, to inhibit its translation. Additionally, we identified that RhoA-GTP could be a potential regulator in MSI1/TNS3-mediated cell migration and morphological changes. In a xenograft animal model, high expression ratio of MSI1 to TNS3 enhanced GBM tumor migration. We also confirmed that MSI1 and TNS3 expressions are mutually exclusive in migratory tumor lesions, and GBM patients with MSI1high/TNS3low pattern tend to have poor clinical outcome. Taken together, our findings suggested a critical role of MSI1-TNS3 axis in regulating GBM migration and highlighted that the ratio of MSI1/TNS3 could predict metastatic and survival outcome of GBM patients.

PMID:
28821879
PMCID:
PMC5562834
DOI:
10.1038/s41598-017-09504-7
[Indexed for MEDLINE]
Free PMC Article

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