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


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Article Info

DATE

2015-11-30

AUTHORS

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

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. More... »

PAGES

3944-3954

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/onc.2015.463

    DOI

    http://dx.doi.org/10.1038/onc.2015.463

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1027092305

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26616853


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