CD99 regulates neural differentiation of Ewing sarcoma cells through miR-34a-Notch-mediated control of NF-κB signaling

S. Ventura, D. N T Aryee, F. Felicetti, A. de Feo, C. Mancarella, M. C. Manara, P. Picci, M. P. Colombo, H. Kovar, A. Carè, K. Scotlandi

Research output: Contribution to journalArticle

Abstract

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.Oncogene advance online publication, 30 November 2015; doi:10.1038/onc.2015.463.

Original languageEnglish
JournalOncogene
DOIs
Publication statusAccepted/In press - Nov 30 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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