Journal
ONCOTARGET
Volume 6, Issue 19, Pages 17805-17816Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4596
Keywords
NF-kappa B; glioblastoma; TRADD; microRNA-31
Categories
Funding
- National Institutes of Health [T32NS048039, R01CA158534, R01CA138517]
- American Brain Tumor Association Basic Research Fellowship in Honor of Paul Fabbri
- Southeastern Brain Tumor Foundation
- UAB Comprehensive Cancer Center
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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-kappa B 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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