Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma

Academic Article

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.
  • Published In

  • Oncotarget  Journal
  • Digital Object Identifier (doi)

    Author List

  • Rajbhandari R; McFarland BC; Patel A; Gerigk M; Kenneth Gray G; Fehling SC; Bredel M; Berbari NF; Kim H; Marks MP
  • Start Page

  • 17805
  • End Page

  • 17816
  • Volume

  • 6
  • Issue

  • 19