title: miRNA expression profiling in migrating glioblastoma cells: regulation of cell migration and invasion by miR-23b via targeting of Pyk2.
abstract: BACKGROUND
  Glioblastoma (GB) is the most common and lethal type of primary brain tumor. Clinical outcome remains poor and is essentially palliative due to the highly invasive nature of the disease. A more thorough understanding of the molecular mechanisms that drive glioma invasion is required to limit dispersion of malignant glioma cells.
  
  
  RESULTS
  We investigated the potential role of differential expression of microRNAs (miRNA) in glioma invasion by comparing the matched large-scale, genome-wide miRNA expression profiles of migrating and migration-restricted human glioma cells. Migratory and migration-restricted cell populations from seven glioma cell lines were isolated and profiled for miRNA expression. Statistical analyses revealed a set of miRNAs common to all seven glioma cell lines that were significantly down regulated in the migrating cell population relative to cells in the migration-restricted population. Among the down-regulated miRNAs, miR-23b has been reported to target potential drivers of cell migration and invasion in other cell types. Over-expression of miR-23b significantly inhibited glioma cell migration and invasion. A bioinformatics search revealed a conserved target site within the 3' untranslated region (UTR) of Pyk2, a non-receptor tyrosine kinase previously implicated in the regulation of glioma cell migration and invasion. Increased expression of miR-23b reduced the protein expression level of Pyk2 in glioma cells but did not significantly alter the protein expression level of the related focal adhesion kinase FAK. Expression of Pyk2 via a transcript variant missing the 3'UTR in miR-23b-expressing cells partially rescued cell migration, whereas expression of Pyk2 via a transcript containing an intact 3'UTR failed to rescue cell migration.
  
  
  CONCLUSIONS
  Reduced expression of miR-23b enhances glioma cell migration in vitro and invasion ex vivo via modulation of Pyk2 protein expression. The data suggest that specific miRNAs may regulate glioma migration and invasion to influence the progression of this disease.
authors: Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona, United States of America. loftus.joseph@mayo.edu
authors: Joseph C
authors: JC
authors: Loftus
authors: Julianna T D
authors: JT
authors: Ross
authors: Kimberly M
authors: KM
authors: Paquette
authors: Vincent M
authors: VM
authors: Paulino
authors: Sara
authors: S
authors: Nasser
authors: Zhongbo
authors: Z
authors: Yang
authors: Jean
authors: J
authors: Kloss
authors: Seungchan
authors: S
authors: Kim
authors: Michael E
authors: ME
authors: Berens
authors: Nhan L
authors: NL
authors: Tran
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
chemical_list: C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D051418:Focal Adhesion Kinase 2