title: miR-124a is frequently down-regulated in glioblastoma and is involved in migration and invasion.
abstract: 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 γ1 (LAMC1) and integrin β1 (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.
authors.affiliation: Cerebral Tumour Research Group, Hormones and Cancer, Kolling Institute of Medical Research, NSW, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Fowler
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomson
authors.forename: Keith
authors.initials: K
authors.lastname: Giles
authors.forename: Sanaz
authors.initials: S
authors.lastname: Maleki
authors.forename: Ellein
authors.initials: E
authors.lastname: Mreich
authors.forename: Helen
authors.initials: H
authors.lastname: Wheeler
authors.forename: Peter
authors.initials: P
authors.lastname: Leedman
authors.forename: Michael
authors.initials: M
authors.lastname: Biggs
authors.forename: Raymond
authors.initials: R
authors.lastname: Cook
authors.forename: Nicholas
authors.initials: N
authors.lastname: Little
authors.forename: Bruce
authors.initials: B
authors.lastname: Robinson
authors.forename: Kerrie
authors.initials: K
authors.lastname: McDonald
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014945:Wound Healing; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: C101203:IQ motif containing GTPase activating protein 1; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D020703:ras GTPase-Activating Proteins