title: TRIM8 downregulation in glioma affects cell proliferation and it is associated with patients survival.
abstract: BACKGROUND
  Human gliomas are a heterogeneous group of primary malignant brain tumors whose molecular pathogenesis is not yet solved. In this regard, a major research effort has been directed at identifying novel specific glioma-associated genes. Here, we investigated the effect of TRIM8 gene in glioma.
  
  
  METHODS
  TRIM8 transcriptional level was profiled in our own glioma cases collection by qPCR and confirmed in the independent TCGA glioma cohort. The association between TRIM8 expression and Overall Survival and Progression-free Survival in TCGA cohort was determined by using uni-multivariable Cox regression analysis. The effect of TRIM8 on patient glioma cell proliferation was evaluated by performing MTT and clonogenic assays. The mechanisms causing the reduction of TRIM8 expression were explored by using qPCR and in vitro assays.
  
  
  RESULTS
  We showed that TRIM8 expression correlates with unfavorable clinical outcome in glioma patients. We found that a restored TRIM8 expression induced a significant reduction of clonogenic potential in U87MG and patient's glioblastoma cells. Finally we provide experimental evidences showing that miR-17 directly targets the 3' UTR of TRIM8 and post-transcriptionally represses the expression of TRIM8.
  
  
  CONCLUSIONS
  Our study provides evidences that TRIM8 may participate in the carcinogenesis and progression of glioma and that the transcriptional repression of TRIM8 might have potential value for predicting poor prognosis in glioma patients.
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. l.micale@operapadrepio.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Micale
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. c.fusco@operapadrepio.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Fusco
authors.affiliation: Biostatistics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. a.fontana@operapadrepio.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, I-71013, San Giovanni Rotondo (FG), Italy. r.barbano@operapadrepio.it.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Barbano
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. bartolomeoaugello@gmail.com.
authors.forename: Bartolomeo
authors.initials: B
authors.lastname: Augello
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. elena.denittis@libero.it.
authors.forename: Pasquelena
authors.initials: P
authors.lastname: De Nittis
authors.affiliation: Biostatistics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. m.copetti@operapadrepio.it.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. mt.pellico@operapadrepio.it.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Pellico
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. bmandriani@gmail.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mandriani
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. dariococciadiferro@gmail.com.|Ph.D program in Experimental and Regenerative Medicine, University of Foggia, Foggia, Italy. dariococciadiferro@gmail.com.
authors.forename: Dario
authors.initials: D
authors.lastname: Cocciadiferro
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, I-71013, San Giovanni Rotondo (FG), Italy. pparrella@operapadrepio.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Parrella
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, I-71013, San Giovanni Rotondo (FG), Italy. fazio@unicampus.it.
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Fazio
authors.affiliation: Pathology Unit, IRCCS Casa Sollievo della Sofferenza, I-71013, San Giovanni Rotondo (FG), Italy. l.dimitri@operapadrepio.it.
authors.forename: Lucia Maria Cecilia
authors.initials: LM
authors.lastname: Dimitri
authors.affiliation: Neurosurgery Unit, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), Italy. v.dangelo@operapadrepio.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: D'Angelo
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. chiara.novielli@unimi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Novielli
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. lidia.larizza@unimi.it.|Laboratory of Medical Cytogenetics and Molecular Genetics, Istituto Auxologico Italiano, Milan, Italy. lidia.larizza@unimi.it.
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
authors.affiliation: Gene Transfer Lab; IRCSS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. antonio.daga@istge.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Daga
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Poliambulatorio Giovanni Paolo II, I-71013, San Giovanni Rotondo (FG), Italy. g.merla@operapadrepio.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Merla
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C418604:TRIM8 protein, human