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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 6
Document type: Journal article
Source: CANCER GENETICS; v. 230, p. 21-27, JAN 2019.
Web of Science Citations: 2
Abstract

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)

FAPESP's process: 15/00524-5 - Influence of miR-10b on proliferation and the invasive potential of osteosarcoma
Grantee:Gabriela Molinari Roberto
Support type: Scholarships in Brazil - Master
FAPESP's process: 14/07118-0 - Effects of rock kinase inhibition in the invasive potential of Ewing Sarcoma cell lines
Grantee:Gabriela Maciel Vieira
Support type: Scholarships in Brazil - Master
FAPESP's process: 14/07117-3 - Evaluation of the expression of microRNAs associated with ROCK kinases and their role in the invasion process in osteosarcoma
Grantee:Lara Elis Alberici Delsin
Support type: Scholarships in Brazil - Master
FAPESP's process: 14/03877-3 - Evaluation of rock kinases and their interaction with microRNAs in bone sarcomas of childhood: implications for tumor progression and invasion
Grantee:María Sol Brassesco Annichini
Support type: Regular Research Grants