CD99
生物
Notch信号通路
微泡
癌症研究
癌变
细胞生物学
飞行1
信号转导
小RNA
转录因子
遗传学
癌症
干细胞
川地34
基因
作者
Selena Ventura,Dave N.T. Aryee,Federica Felicetti,Alessandra De Feo,Caterina Mancarella,Maria Cristina Manara,Piero Picci,Mario P. Colombo,Heinrich Kovar,Alessandra Carè,Katia Scotlandi
出处
期刊:Oncogene
[Springer Nature]
日期:2015-11-30
卷期号:35 (30): 3944-3954
被引量:48
摘要
Sarcomas are mesenchymal tumors characterized by blocked differentiation process. In Ewing sarcoma (EWS) both CD99 and EWS-FLI1 concur to oncogenesis and inhibition of differentiation. Here, we demonstrate that uncoupling CD99 from EWS-FLI1 by silencing the former, nuclear factor-κB (NF-κB) signaling is inhibited and the neural differentiation program is re-established. NF-κB inhibition passes through miR-34a-mediated repression of Notch pathway. CD99 counteracts EWS-FLI1 in controlling NF-κB signaling through the miR-34a, which is increased and secreted into exosomes released by CD99-silenced EWS cells. Delivery of exosomes from CD99-silenced cells was sufficient to induce neural differentiation in recipient EWS cells through miR-34a inhibition of Notch-NF-κB signaling. Notably, even the partial delivery of CD99 small interfering RNA may have a broad effect on the entire tumor cell population owing to the spread operated by their miR-34a-enriched exosomes, a feature opening to a new therapeutic option.
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