The role of miR-451 in the switching between proliferation and migration in malignant glioma cells: AMPK signaling, mTOR modulation and Rac1 activation required
Glioblastoma multiforme (GBM), WHO gradeĀ 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.
Document Type: Research Article
Affiliations: 1: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China 2: Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China 3: Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Publication date: 01 June 2017
- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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