CD99 Regulates Neural Differentiation of Ewing Sarcoma Cells Through MiR-34a-Notch-mediated Control of NF-κB Signaling

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2015 Dec 1

PMID 26616853

Citations 42

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 Care

K Scotlandi

Affiliations

Soon will be listed here.

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.

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