miR-214-3p Is Commonly Downregulated by EWS-FLI1 and by CD99 and Its Restoration Limits Ewing Sarcoma Aggressiveness

Cancers

卷:14

Giuseppe Bianchi¹  Benedetta Spazzoli¹  Lisa Ciuffarin²  Katia Scotlandi²  Cristina Ferrari²  Elisa Simonetti²  Evelin Pellegrini²  Michela Pasello²  Laura Pazzaglia²  Fabio Mangiagli²  Alessandra De Feo² 

[1] IRCCS Istituto Ortopedico Rizzoli, Third Orthopaedic Clinic and Traumatology, 40136 Bologna, Italy;

[2] SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy;

关键词: Ewing sarcoma;    miR-214-3p;    HMGA1;    EWS-FLI1;    CD99;    migration;   

DOI  :  10.3390/cancers14071762

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown