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miR-214-3p Is Commonly Downregulated by EWS-FLI1 and by CD99 and Its Restoration Limits Ewing Sarcoma Aggressiveness.
De Feo, Alessandra; Pazzaglia, Laura; Ciuffarin, Lisa; Mangiagli, Fabio; Pasello, Michela; Simonetti, Elisa; Pellegrini, Evelin; Ferrari, Cristina; Bianchi, Giuseppe; Spazzoli, Benedetta; Scotlandi, Katia.
Afiliação
  • De Feo A; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
  • Pazzaglia L; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
  • Ciuffarin L; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
  • Mangiagli F; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
  • Pasello M; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
  • Simonetti E; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
  • Pellegrini E; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
  • Ferrari C; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
  • Bianchi G; IRCCS Istituto Ortopedico Rizzoli, Third Orthopaedic Clinic and Traumatology, 40136 Bologna, Italy.
  • Spazzoli B; IRCCS Istituto Ortopedico Rizzoli, Third Orthopaedic Clinic and Traumatology, 40136 Bologna, Italy.
  • Scotlandi K; SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
Cancers (Basel) ; 14(7)2022 Mar 30.
Article em En | MEDLINE | ID: mdl-35406534
ABSTRACT
Ewing's sarcoma (EWS), an aggressive pediatric bone and soft-tissue sarcoma, has a very stable genome with very few genetic alterations. Unlike in most cancers, the progression of EWS appears to depend on epigenetic alterations. EWS-FLI1 and CD99, the two hallmarks of EWS, are reported to severely impact the malignancy of EWS cells, at least partly by regulating the expression of several types of non-coding RNAs. Here, we identify miR-214-3p as a common mediator of either EWS-FLI1 or CD99 by in silico analysis. MiR-214-3p expression was lower in EWS cells and in clinical samples than in bone marrow mesenchymal stem cells, and this miRNA was barely expressed in metastatic lesions. Silencing of EWS-FLI1 or CD99 restored the expression of miR-214-3p, leading to a reduced cell growth and migration. Mechanistically, miR-214-3p restoration inhibits the expression of the high-mobility group AT-hook 1 (HMGA1) protein, a validated target of miR-214-3p and a major regulator of the transcriptional machinery. The decrease in HMGA1 expression reduced the growth and the migration of EWS cells. Taken together, our results support that the miR-214-3p is constitutively repressed by both EWS-FLI1 and CD99 because it acts as an oncosuppressor limiting the dissemination of EWS cells.
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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália