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

Authors

Rajani Rajbhandari
Braden C McFarland
Ashish Patel
Magda Gerigk
G Kenneth Gray
Samuel C Fehling
Markus Bredel
Nicolas F Berbari
Hyunsoo Kim, The Jackson LaboratoryFollow
Margaret P Marks
Gordon P Meares
Tanvi Sinha
Jeffrey Chuang, The Jackson LaboratoryFollow
Etty N Benveniste
Susan E Nozell

Document Type

Article

Publication Date

7-10-2015

JAX Location

Reprint Collection

JAX Source

Oncotarget 2015 Jul 10; 6(19):17805-16.

Volume

6

Issue

19

First Page

17805

Last Page

17816

ISSN

1949-2553

PMID

26164206

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. Oncotarget 2015 Jul 10; 6(19):17805-16.

Recommended Citation

Rajbhandari R, McFarland B, Patel A, Gerigk M, Gray G, Fehling S, Bredel M, Berbari N, Kim H, Marks M, Meares G, Sinha T, Chuang J, Benveniste E, Nozell S. Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma. Oncotarget 2015 Jul 10; 6(19):17805-16.