MiR-708-5p is inversely associated with EWS/FLI1 Ewing sarcoma but does not represent a prognostic predictor

Autor(es)

Roberto, Gabriela Molinari ^[1] ; Vieira, Gabriela Maciel ^[2] ; Alberici Delsin, Lara Elis ^[2] ; Silva, Marcela de Oliveira ^[3] ; Hakime, Rodrigo Guedes ^[4] ; Engel, Edgard Eduard ^[5] ; Scrideli, Carlos Alberto ^[6] ; Tone, Luiz Gonzaga ^[6] ; Brassesco, Maria Sol ^[5]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Sch Med, Reg Blood Ctr, Av Bandeirantes 3, 900 Bairro Monte Alegre, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Genet, Av Bandeirantes 3, 900 Bairro Monte Alegre, BR-14040901 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Cell Biol, Av Bandeirantes 3, 900 Bairro Monte Alegre, BR-14040901 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Dept Biol, Av Bandeirantes 3, 900 Bairro Monte Alegre, BR-14040901 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biomech Med & Rehabil Locomotor Syst, Av Bandeirantes 3, 900 Bairro Monte Alegre, BR-14040901 Ribeirao Preto, SP - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pediat, Av Bandeirantes 3, 900 Bairro Monte Alegre, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CANCER GENETICS; v. 230, p. 21-27, JAN 2019.
• Citações Web of Science: 2

Resumo

Background: Overall survival of Ewing sarcoma (EWS) remains poor and less than 30% of patients with metastatic or recurrent disease survive despite current treatments. Thus, there is a constant search for new biomarkers for diagnosis, prognosis and prediction of therapy. Numerous studies have reported the abnormal expression of miR-708-5p in tumors of different origins. However, its role in EWS remains unclear. Procedure: qRT-PCR was performed in nineteen consecutive EWS samples and twelve non tumor bone samples from age-matched controls. Functional assays were performed in SK-ES-1 cells transfected with miR-708 lentiviral-based vectors and results analyzed in terms of clonogenicity, migration, invasion and western blot. Results: We show that miR-708-5p is downregulated in EWS tissues though no associations with any prognostic features such as HUVOS grade, event or survival were found in our cohort. Nonetheless, expression levels of this micro-RNA were inversely associated with the presence of the EWS/FLI1 translocation. When miR-708-5p was transfected into the SK-ES-1 cell line, it did not affect migration or clonogenicity, but promoted a significant increase on the invasive potential of cells endorsed with high expression of MMP2. Conclusions: Taken together, our results suggest that despite downregulated in EWS samples, this miRNA might represent a secondary genetic alteration derived from the pleiotropic cellular effects of the abnormal EWS/FLI1 transcription factor that does not affect tumor growth but instead, is related with the promotion of tumor invasion, not being suitable for future therapeutic intervention. (AU)

• Processo FAPESP: 15/00524-5 - Influência do miR-10b na proliferação e capacidade invasiva de osteossarcoma
• Beneficiário: Gabriela Molinari Roberto
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/07118-0 - Efeitos da inibição das quinases rock no potencial invasivo de linhagens celulares de Sarcoma de Ewing
• Beneficiário: Gabriela Maciel Vieira
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/07117-3 - Avaliação de microRNAs associados às quinases ROCK em osteosarcoma e seu papel no processo de invasão celular
• Beneficiário: Lara Elis Alberici Delsin
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/03877-3 - Avaliação das quinases rock e interações com microRNAs em sarcomas ósseos da infância: implicações no processo de invasão e progressão tumoral
• Beneficiário: María Sol Brassesco Annichini
• Linha de fomento: Auxílio à Pesquisa - Regular