title: Differential expression and clinical significance of three inflammation-related microRNAs in gangliogliomas.
abstract: OBJECTIVE
  miR21, miR146, and miR155 represent a trio of microRNAs which has been shown to play a key role in the regulation of immune and inflammatory responses. In the present study, we investigated the differential expression and clinical significance of these three miRNAs in glioneuronal tumors (gangliogliomas, GGs) which are characterized by prominent activation of the innate immune response.
  
  
  METHODS
  The expression levels of miR21, miR146, and miR155 were evaluated using Taqman PCR in 34 GGs, including 15 cases with sufficient amount of perilesional cortex. Their expression was correlated with the tumor features and the clinical history of epilepsy. In addition, in situ hybridization was used to evaluate their cellular distribution in both tumor and peritumoral cortex.
  
  
  RESULTS
  Increased expression of miR146a was observed in both tumor and peritumoral cortex compared to control samples. miR146a was detected in both neuronal and astroglial cells. Tumor and peritumoral miR146a expression was negatively correlated with frequency of seizures and the density of activated microglial cells. Neuronal and astroglial expression was observed for both miR21 and miR155 with increased expression of miR21 within the tumor and miR155 in the peritumoral region. Negative correlations were observed between the miRNA levels and the expression of putative targets within the astroglial component of the tumor.
  
  
  CONCLUSIONS
  We report a differential regulation of three miRNAs, known to be related to inflammation, in both tumor and peritumoral cortex of patients with GG. Moreover, our findings suggest a functional relationship between miR146a expression and epilepsy, either directly in epileptogenesis or as modulation of seizure activity.
authors.affiliation: Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.s.prabowo@amc.uva.nl.
authors.forename: A S
authors.initials: AS
authors.lastname: Prabowo
authors.affiliation: Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. j.g.scheppingen@amc.uva.nl.
authors.forename: J
authors.initials: J
authors.lastname: van Scheppingen
authors.affiliation: Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.m.iyer@amc.uva.nl.
authors.forename: A M
authors.initials: AM
authors.lastname: Iyer
authors.affiliation: Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. j.j.anink@amc.uva.nl.
authors.forename: J J
authors.initials: JJ
authors.lastname: Anink
authors.affiliation: Department of Pathology, Rudolf Magnus Institute for Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. w.g.m.spliet@umcutrecht.nl.
authors.forename: W G M
authors.initials: WG
authors.lastname: Spliet
authors.affiliation: Department of Neurosurgery, Rudolf Magnus Institute for Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. p.v.rijen@umcutrecht.nl.
authors.forename: P C
authors.initials: PC
authors.lastname: van Rijen
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.y.n.schouten@amc.uva.nl.
authors.forename: A Y N
authors.initials: AY
authors.lastname: Schouten-van Meeteren
authors.affiliation: Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. e.aronica@amc.uva.nl.|SEIN - Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands. e.aronica@amc.uva.nl.|Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands. e.aronica@amc.uva.nl.
authors.forename: E
authors.initials: E
authors.lastname: Aronica
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004827:Epilepsy / Q000209:etiology; D005260:Female; D018303:Ganglioglioma / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D019394:Ki-67 Antigen; C542542:MIRN146 microRNA, human; C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins