title: MicroRNA-145 Promotes the Phenotype of Human Glioblastoma Cells Selected for Invasion.
abstract: OBJECTIVE
  Novel treatment strategies aiming to eliminate or attenuate the invasive phenotype of glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, could offer a profound therapeutic benefit to patients. We previously demonstrated one method to create invasive sub-populations of GBM cells (IM3 cells) and a positive regulatory role for the miR-143/-145 locus in enhancing the invasion of GBM cells. Herein, we investigated the correlation between miR-145 and srGAP1 (SLIT-ROBO Rho GTPase-activating protein1) that is purported to be a target of miR-145 and involved in migration and invasion.
  
  
  METHODS
  IM3 cells were created by a serial selection by using Boyden chambers®. Antisense-miR-145 was transfected into IM3 cells by using lipofectamine 2000. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were employed to analyze the expression of srGAP1.
  
  
  RESULTS
  The invasiveness of U87-IM3 and U251-IM3 is attenuated by transfection of antisense miR-145. In addition, srGAP1 was down-regulated in U87-IM3 and U251-IM3 cells compared to parental cells.
  
  
  CONCLUSIONS
  The elevated miR-145 present in invasive glioblastoma cells (IM3 cells) targets and down-regulated srGAP1, thereby allowing downstream G-proteins to remain in their active state and promote the observed invasive phenotype.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, TX, U.S.A. lgtoussaint@medicine.tamhsc.edu swkoo@tamhsc.edu.
authors.forename: Sunwoo
authors.initials: S
authors.lastname: Koo
authors.affiliation: Genomics and Bioinformatic Services, Texas A&M AgriLife Research, College Station, Bryan, TX, U.S.A.
authors.forename: Gail
authors.initials: G
authors.lastname: Martin
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, Bryan, TX, U.S.A. The Texas Brain and Spine Institute, Bryan, TX, U.S.A. lgtoussaint@medicine.tamhsc.edu swkoo@tamhsc.edu.
authors.forename: L Gerard
authors.initials: LG
authors.lastname: Toussaint
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology
chemical_list: D020690:GTPase-Activating Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C582067:SRGAP1 protein, human
keywords: SLIT-ROBO; glioblastoma; miRNA-145; srGAP