肿瘤抑制性微小RNA-31的缺失增强了胶质母细胞瘤中的TRADD/NF-κB信号传导。
Loss of tumor suppressive microRNA-31 enhances TRADD/NF-κB signaling in glioblastoma.
作者信息
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, Nozell Susan E
机构信息
Departments of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Radiation Oncology at the University of Alabama at Birmingham, Birmingham, Alabama, USA.
出版信息
Oncotarget. 2015 Jul 10;6(19):17805-16. doi: 10.18632/oncotarget.4596.
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.
胶质母细胞瘤（GBM）是中枢神经系统的致命肿瘤。大多数GBM在9p21.3处表现出细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）和细胞周期蛋白依赖性激酶抑制剂2B（CDKN2B）肿瘤抑制基因的纯合缺失，尽管单独缺失CDKN2A/B不足以驱动胶质瘤发生。MIR31HG编码微小RNA-31（miR-31），是一种位于9p21.3与CDKN2A/B相邻位置的新型非编码肿瘤抑制基因。我们已经确定，在所有GBM中，超过72%的miR-31表达受损，对于患者而言，这预示着生存时间显著缩短，且与CDKN2A/B状态无关。我们发现miR-31通过靶向其上游激活因子肿瘤坏死因子受体相关死亡结构域蛋白（TRADD）来抑制核因子κB（NF-κB）信号通路。此外，在重新导入miR-31后，动物模型中的肿瘤负荷显著降低，生存时间延长。因此，我们的研究确定miR-31缺失是GBM中一种新型的非编码肿瘤驱动事件。
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