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The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required

  • Authors:
    • Kai Zhao
    • Leilei Wang
    • Tao Li
    • Meng Zhu
    • Chen Zhang
    • Lei Chen
    • Pengfei Zhao
    • Hua Zhou
    • Shengping Yu
    • Xuejun Yang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1989-1999
    |
    Published online on: April 21, 2017
       https://doi.org/10.3892/ijo.2017.3973
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Abstract

Glioblastoma multiforme (GBM), WHO grade IV astrocytoma, is the most common primary neoplasm of the central nervous system (CNS) and has the highest malignancy and mortality rates. The invasive nature of GBM complicates surgical resection and restricts chemotherapeutic access, contributing to poor patient prognosis. The migration of tumor cells is closely related to the tumor cell proliferation. The acquisition of migratory capability, in addition to intracellular factors, is proposed to be a crucial mechanism during the progression of invasion. Using qRT-PCR analysis, we determined that the expression of miR-451 in glioma tissue was lower than in control brain tissue, especially in the central portions of the tumor. In glioma cell lines, we found that decreased miR-451 expression suppressed tumor cell proliferation but enhanced migration with a concomitant low level of CAB39/AMPK/mTOR pathway activation and high level of Rac1/cofilin pathway activation, respectively. Notably, the effect of miR-451 on cytological behavior and on the activation of mTOR and Rac1 was limited when AMPKα1 expression was knocked-down with a synthetic shRNA. We suggest that the glioma microenvironment results in heterogeneity of miR-451 expression. Our data indicated that miR-451 relays environmental signals by upregulating the activity of AMPK signaling, thereby modulating the activation of mTOR and Rac1/cofilin which, in turn, play key roles in glioma cell proliferation and migration, respectively. Our results highlight the need to consider opposing roles of a therapeutic target which, while suppressing tumor cell proliferation, could also promote cell infiltration.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao K, Wang L, Li T, Zhu M, Zhang C, Chen L, Zhao P, Zhou H, Yu S, Yang X, Yang X, et al: The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required. Int J Oncol 50: 1989-1999, 2017.
APA
Zhao, K., Wang, L., Li, T., Zhu, M., Zhang, C., Chen, L. ... Yang, X. (2017). The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required. International Journal of Oncology, 50, 1989-1999. https://doi.org/10.3892/ijo.2017.3973
MLA
Zhao, K., Wang, L., Li, T., Zhu, M., Zhang, C., Chen, L., Zhao, P., Zhou, H., Yu, S., Yang, X."The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required". International Journal of Oncology 50.6 (2017): 1989-1999.
Chicago
Zhao, K., Wang, L., Li, T., Zhu, M., Zhang, C., Chen, L., Zhao, P., Zhou, H., Yu, S., Yang, X."The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required". International Journal of Oncology 50, no. 6 (2017): 1989-1999. https://doi.org/10.3892/ijo.2017.3973
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao K, Wang L, Li T, Zhu M, Zhang C, Chen L, Zhao P, Zhou H, Yu S, Yang X, Yang X, et al: The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required. Int J Oncol 50: 1989-1999, 2017.
APA
Zhao, K., Wang, L., Li, T., Zhu, M., Zhang, C., Chen, L. ... Yang, X. (2017). The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required. International Journal of Oncology, 50, 1989-1999. https://doi.org/10.3892/ijo.2017.3973
MLA
Zhao, K., Wang, L., Li, T., Zhu, M., Zhang, C., Chen, L., Zhao, P., Zhou, H., Yu, S., Yang, X."The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required". International Journal of Oncology 50.6 (2017): 1989-1999.
Chicago
Zhao, K., Wang, L., Li, T., Zhu, M., Zhang, C., Chen, L., Zhao, P., Zhou, H., Yu, S., Yang, X."The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required". International Journal of Oncology 50, no. 6 (2017): 1989-1999. https://doi.org/10.3892/ijo.2017.3973
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