Abstract
Background: Glioblastoma Multiforme (GBM) is the most common and lethal primary tumor of the brain. GBM is associated with one of the worst 5-year survival rates among all human cancers, despite much effort in different modes of treatment. Results: Here, we demonstrate specific GBM cancer phenotypes that are governed by modifications to the MAPAKAP network. We then demonstrate a novel regulation mode by which a set of five key factors of the MAPKAP pathway are regulated by the same microRNA, hsa-miR-9. We demonstrate that hsa-miR-9 overexpression leads to MAPKAP signaling inhibition, partially by interfering with the MAPK14/MAPKAP3 complex. Further, hsamiR-9 overexpression initiates re-arrangement of actin filaments, which leads us to hypothesize a mechanism for the observed phenotypic shift. Conclusion: The work presented here exposes novel microRNA features and situates hsa-miR-9 as a therapeutic target, which governs metastasis and thus determines prognosis in GBM through MAPKAP signaling.
Original language | English |
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Pages (from-to) | 23170-23181 |
Number of pages | 12 |
Journal | Oncotarget |
Volume | 7 |
Issue number | 17 |
DOIs | |
State | Published - 26 Apr 2016 |
Keywords
- Cytoskeleton
- Glioblastoma
- MAPKAP signaling
- Metastasis
- Pathways
- hsa-miR9
All Science Journal Classification (ASJC) codes
- Oncology