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MiR-301a is activated by the Wnt/β-catenin pathway and promotes glioma cell invasion by suppressing SEPT7.
- Source :
-
Neuro-oncology [Neuro Oncol] 2016 Sep; Vol. 18 (9), pp. 1288-96. Date of Electronic Publication: 2016 Mar 22. - Publication Year :
- 2016
-
Abstract
- Background: miR-301a is frequently dysregulated and specific to human tumors, playing a critical role in tumorigenesis; however, the exact functions and regulatory mechanisms of miR-301a in glioma cells remain largely unknown. Herein, we show that miR-301a activated by the Wnt/β-catenin pathway promoted the invasion of glioma cells by directly targeting SEPT7.<br />Methods: Biochemical, luciferase reporter, and hromatin immunoprecipitation PCR assays characterized the function and regulatory mechanisms of miR-301a in glioma invasion.<br />Results: Initially, we detected the expression of miR-301a in glioma tissues and identified that miR-301a had increased, with ascending grades of the tumor. Furthermore, high levels of miR-301a were associated with a poorer prognosis in glioma patients. It is important to note that the Wnt/β-catenin/TCF4 pathway enhanced miR-301a expression by binding to the promoter region. To determine the oncogenic functions of miR-301a in glioma, SEPT7 was supported as the direct target gene. In addition, the Wnt/β-catenin pathway repressed SEPT7 expression, which was dependent on miR-301a in glioma cells. Finally, miR-301a was activated by Wnt/β-catenin and then promoted invasion of glioma cells by inhibiting the expression of SEPT7 in vitro and in vivo.<br />Conclusions: Our findings revealed the mechanism of action for miR-301a in tumor cell invasion. Moreover, the Wnt/miR-301a/SEPT7 signaling axis might be a novel target in treating glioma.<br /> (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Apoptosis
Cell Cycle Proteins genetics
Cell Proliferation
Gene Expression Regulation, Neoplastic
Glioma genetics
Glioma metabolism
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Staging
Prognosis
Septins genetics
Survival Rate
Tumor Cells, Cultured
Wnt Proteins genetics
Xenograft Model Antitumor Assays
beta Catenin genetics
Cell Cycle Proteins metabolism
Glioma pathology
MicroRNAs genetics
Septins metabolism
Wnt Proteins metabolism
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1523-5866
- Volume :
- 18
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Neuro-oncology
- Publication Type :
- Academic Journal
- Accession number :
- 27006177
- Full Text :
- https://doi.org/10.1093/neuonc/now044