title: Regulation of IL-8 gene expression in gliomas by microRNA miR-93.
abstract: BACKGROUND
  Different strategies have been proposed to target neoangiogenesis in gliomas, besides those targeting Vascular Endothelial Growth Factor (VEGF). The chemokine Interleukin-8 (IL-8) has been shown to possess both tumorigenic and proangiogenic properties. Although different pathways of induction of IL-8 gene expression have been already elucidated, few data are available on its post-transcriptional regulation in gliomas.
  
  
  METHODS
  Here we investigated the role of the microRNA miR-93 on the expression levels of IL-8 and other pro-inflammatory genes by RT-qPCR and Bio-Plex analysis. We used different disease model systems, including clinical samples from glioma patients and two glioma cell lines, U251 and T98G.
  
  
  RESULTS
  IL-8 and VEGF transcripts are highly expressed in low and high grade gliomas in respect to reference healthy brain; miR-93 expression is also increased and inversely correlated with transcription of IL-8 and VEGF genes. Computational analysis showed the presence of miR-93 consensus sequences in the 3'UTR region of both VEGF and IL-8 mRNAs, predicting possible interaction with miR-93 and suggesting a potential regulatory role of this microRNA. In vitro transfection with pre-miR-93 and antagomiR-93 inversely modulated VEGF and IL-8 gene expression and protein release when the glioma cell line U251 was considered. Similar data were obtained on IL-8 gene regulation in the other glioma cell line analyzed, T98G. The effect of pre-miR-93 and antagomiR-93 in U251 cells has been extended to the secretion of a panel of cytokines, chemokines and growth factors, which consolidated the concept of a role of miR-93 in IL-8 and VEGF gene expression and evidenced a potential regulatory role also for MCP-1 and PDGF (also involved in angiogenesis).
  
  
  CONCLUSIONS
  In conclusion, our results suggest an increasing role of miR-93 in regulating the level of expression of several genes involved in the angiogenesis of gliomas.
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara n.74, 44121, Ferrara, Italy. enrica.fabbri@unife.it.
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara n.74, 44121, Ferrara, Italy. eleonora.brognara@unife.it.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brognara
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara n.74, 44121, Ferrara, Italy. giulia.montagner@unife.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Montagner
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Molecular Pathology, University-Hospital of Verona, P.le A Stefani n.1, 37126, Verona, Italy. claudio.ghimenton@ospedaleuniverona.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ghimenton
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Molecular Pathology, University-Hospital of Verona, P.le A Stefani n.1, 37126, Verona, Italy. albino.eccher@ospedaleuniverona.it.
authors.forename: Albino
authors.initials: A
authors.lastname: Eccher
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Molecular Pathology, University-Hospital of Verona, P.le A Stefani n.1, 37126, Verona, Italy. cinzia_cantu@hotmail.com.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cantù
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Molecular Pathology, University-Hospital of Verona, P.le A Stefani n.1, 37126, Verona, Italy. susanna.khalil89@gmail.com.
authors.forename: Susanna
authors.initials: S
authors.lastname: Khalil
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Molecular Pathology, University-Hospital of Verona, P.le A Stefani n.1, 37126, Verona, Italy. valentino.bezzerri@gmail.com.
authors.forename: Valentino
authors.initials: V
authors.lastname: Bezzerri
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Molecular Pathology, University-Hospital of Verona, P.le A Stefani n.1, 37126, Verona, Italy. lisa.provezza@univr.it.
authors.forename: Lisa
authors.initials: L
authors.lastname: Provezza
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara n.74, 44121, Ferrara, Italy. nicoletta.bianchi@unife.it.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara n.74, 44121, Ferrara, Italy. alessia.finotti@unife.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Finotti
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara n.74, 44121, Ferrara, Italy. monica.borgatti@unife.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.affiliation: Department of Neurosciences, University-Hospital of Verona, P.le A Stefani n.1, Verona, 37126, Italy. giuseppe.moretto@ospedaleuniverona.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Moretto
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Molecular Pathology, University-Hospital of Verona, P.le A Stefani n.1, 37126, Verona, Italy. marco.chilosi@univr.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Molecular Pathology, University-Hospital of Verona, P.le A Stefani n.1, 37126, Verona, Italy. giulio.cabrini@univr.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Cabrini
authors.affiliation: Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara n.74, 44121, Ferrara, Italy. gam@unife.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D016209:Interleukin-8 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008954:Models, Biological; D060787:Neoplasm Grading; D009690:Nucleic Acid Conformation; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016209:Interleukin-8; C543350:MIRN93 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A