Journal
EUROPEAN JOURNAL OF CANCER
Volume 47, Issue 6, Pages 953-963Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2010.11.026
Keywords
miR-124a; GBM; Migration; Invasion; Overall survival; IQGAP1; LAMC1; ITGB1
Categories
Funding
- Cancer Council of NSW
- Andrew Olle Memorial Trust
- Sydney Neuro-oncology Group
- NHMRC
- Royal Australasian College of Surgeons
- Synthes
- Neurosurgical Society of Australasia
- Cancer Institute NSW
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Glioblastoma (GBM) represents a formidable clinical challenge for both patients and treating physicians. Due to better local treatments and prolonged patient survival, remote recurrences are increasingly observed, underpinning the importance of targeting tumour migration and attachment. Aberrant expression of microRNA (miRNA) is commonly associated with cancer and loss of miR-124a has previously been implicated to function as a tumour suppressor. The assessment of miR-124a in clinical specimens has been limited and a potential role in migration and invasion has been unexplored until now. We measured the expression levels of mature miR-124a in a retrospective series of 119 cases of histologically confirmed GBM and found its expression was markedly lower in over 80% of the GBM clinical specimens compared to normal brain tissue. The level of reduction in the clinical cohort varied significantly and patients with lower than the average miR-124a expression levels displayed shorter survival times. Endogenous miR-124a expression and the protein expression of three of its targets; IQ motif containing GTPase activating protein 1 (IQGAP1), laminin gamma 1 (LAMC1) and integrin beta 1 (ITGB1) were significantly reciprocally associated in the majority of the clinical cases. We confirmed this association in our in vitro model. Functionally, the ectopic expression of mature miR-124a in a GBM cell line resulted in significant inhibition of migration and invasion, demonstrating a role for miR-124a in promoting tumour invasiveness. Our results suggest that miR-124a may play a role in GBM migration, and that targeted delivery of miR-124a may be a novel inhibitor of GBM invasion. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.
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