Oncotarget

Research Papers:

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

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

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Oncotarget. 2015; 6:17805-17816. https://doi.org/10.18632/oncotarget.4596

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Abstract

Rajani Rajbhandari1,*, Braden C. McFarland1,*, Ashish Patel1, Magda Gerigk1, G. Kenneth Gray1, Samuel C. Fehling1, Markus Bredel2, Nicolas F. Berbari1, Hyunsoo Kim3, Margaret P. Marks1, Gordon P. Meares1, Tanvi Sinha1, Jeffrey Chuang3, Etty N. Benveniste1 and Susan E. Nozell1

1 Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA

2 Radiation Oncology at the University of Alabama at Birmingham, Birmingham, Alabama, USA

3 Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA

* These authors have contributed equally to this work

Correspondence to:

Susan Nozell, email:

Keywords: NF-κB, glioblastoma, TRADD, microRNA-31

Received: June 12, 2015 Accepted: June 17, 2015 Published: June 23, 2015

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.


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