title: Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma.
abstract: Glioblastomas (GBMs) are deadly tumors of the central nervous system. Most GBM exhibit homozygous deletions of the CDKN2A and CDKN2B tumor suppressors at 9p21.3, although loss of CDKN2A/B alone is insufficient to drive gliomagenesis. MIR31HG, which encodes microRNA-31 (miR-31), is a novel non-coding tumor suppressor positioned adjacent to CDKN2A/B at 9p21.3. We have determined that miR-31 expression is compromised in >72% of all GBM, and for patients, this predicts significantly shortened survival times independent of CDKN2A/B status. We show that miR-31 inhibits NF-κB signaling by targeting TRADD, its upstream activator. Moreover, upon reintroduction, miR-31 significantly reduces tumor burden and lengthens survival times in animal models. As such, our work identifies loss of miR-31 as a novel non-coding tumor-driving event in GBM.
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Rajani
authors.initials: R
authors.lastname: Rajbhandari
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Braden C
authors.initials: BC
authors.lastname: McFarland
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Patel
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Magda
authors.initials: M
authors.lastname: Gerigk
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: G Kenneth
authors.initials: GK
authors.lastname: Gray
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Fehling
authors.affiliation: Radiation Oncology at the University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Bredel
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Berbari
authors.affiliation: Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Marks
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Meares
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Sinha
authors.affiliation: Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chuang
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Etty N
authors.initials: EN
authors.lastname: Benveniste
authors.affiliation: Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Nozell
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D053199:TNF Receptor-Associated Death Domain Protein / Q000378:metabolism
chemical_list: C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D053199:TNF Receptor-Associated Death Domain Protein
keywords: NF-κB; TRADD; glioblastoma; microRNA-31