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MicroRNA-451 Inhibits Migration of Glioblastoma while Making It More Susceptible to Conventional Therapy

1
Department of Neurosurgery, Harvey Cushing Neuro-oncology Laboratories, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
2
Department of Neurological Surgery, Kagawa University Hospital, Miki-cho, 761-0793 Kagawa, Japan
3
Division of Neurosurgery, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
4
Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Non-Coding RNA 2019, 5(1), 25; https://doi.org/10.3390/ncrna5010025
Received: 21 December 2018 / Revised: 8 March 2019 / Accepted: 11 March 2019 / Published: 15 March 2019
(This article belongs to the Special Issue Non-Coding RNA and Brain Tumors)
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Abstract

Malignant glioblastoma (GBM, glioma) is the most common and aggressive primary adult brain tumor. The prognosis of GBM patients remains poor, despite surgery, radiation and chemotherapy. The major obstacles for successful remedy are invasiveness and therapy resistance of GBM cells. Invasive glioma cells leave primary tumor core and infiltrate surrounding normal brain leading to inevitable recurrence, even after surgical resection, radiation and chemotherapy. Therapy resistance allowing for selection of more aggressive and resistant sub-populations including GBM stem-like cells (GSCs) upon treatment is another serious impediment to successful treatment. Through their regulation of multiple genes, microRNAs can orchestrate complex programs of gene expression and act as master regulators of cellular processes. MicroRNA-based therapeutics could thus impact broad cellular programs, leading to inhibition of invasion and sensitization to radio/chemotherapy. Our data show that miR-451 attenuates glioma cell migration in vitro and invasion in vivo. In addition, we have found that miR-451 sensitizes glioma cells to conventional chemo- and radio-therapy. Our data also show that miR-451 is regulated in vivo by AMPK pathway and that AMPK/miR-451 loop has the ability to switch between proliferative and migratory pattern of glioma cells behavior. We therefore postulate that AMPK/miR-451 negative reciprocal feedback loop allows GBM cells/GSCs to adapt to tumor “ecosystem” by metabolic and behavioral flexibility, and that disruption of such a loop reduces invasiveness and diminishes therapy resistance. View Full-Text
Keywords: glioblastoma; microRNA; AMPK; invasiveness; therapy resistance glioblastoma; microRNA; AMPK; invasiveness; therapy resistance
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Ogawa, D.; Ansari, K.; Nowicki, M.O.; Salińska, E.; Bronisz, A.; Godlewski, J. MicroRNA-451 Inhibits Migration of Glioblastoma while Making It More Susceptible to Conventional Therapy. Non-Coding RNA 2019, 5, 25.

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