Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma.
Oncotarget 2015 Jul 10; 6(19):17805-16.
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.
Rajbhandari, Rajani; McFarland, Braden C; Patel, Ashish; Gerigk, Magda; Gray, G Kenneth; Fehling, Samuel C; Bredel, Markus; Berbari, Nicolas F; Kim, Hyunsoo; Marks, Margaret P; Meares, Gordon P; Sinha, Tanvi; Chuang, Jeffrey; Benveniste, Etty N; and Nozell, Susan E, "Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma." (2015). Faculty Research 2015. 125.