ROCK1-PredictedmicroRNAs Dysregulation Contributes to Tumor Progression in Ewing Sarcoma

Autor(es)

Roberto, G. M. ^[1] ; Delsin, L. E. A. ^[2] ; Vieira, G. M. ^[2] ; Silva, M. O. ^[3] ; Hakime, R. G. ^[4] ; Gava, N. F. ^[5] ; Engel, E. E. ^[5] ; Scrideli, C. A. ^[6] ; Tone, L. G. ^[6] ; Brassesco, Maria Sol ^{[5, 7]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Sch Med, Reg Blood Ctr, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Genet, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Cell Biol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Dept Biol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biomech Med & Rehabil Locomotor Syst, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pediat, Sao Paulo - Brazil

^[7] Univ Sao Paulo, FFCLRP, Dept Biol, Av Bandeirantes, 3900 Bairro Monte Alegre, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Pathology & Oncology Research; v. 26, n. 1, p. 133-139, JAN 2020.
• Citações Web of Science: 4

Resumo

Over the last decade, the rho-associated kinases and several metastasis-associated microRNAs have emerged as important contributors of tumor invasion. However, despite prominence, our understanding of their involvement in the metastatic potential of Ewing Sarcoma (EWS) is incomplete. The expression profiles of ROCK1 or ROCK2 and miR-124-3p, miR-138-5p, miR-139-5p, miR-335-5p and miR-584-5p (all of which were previously predicted or validated to regulate these kinases) were evaluated through qRT-PCR and associated with clinical parameters. In vitro assays to evaluate colony formation and invasion/migration capacieties were performed on SK-ES-1 cells transfected with pre-miR mimics. ROCK1 expression was significantly reduced in EWS tissues, though there was no association with pathological parameters. miR-124-3p, miR-139-5p and miR-335-3p were also found significantly downregulated and positively correlated with ROCK1. Stratification indicated an association between lower levels of miR-139-5p and miR-584-5p with disease progression (p < 0.05), while reduced expression of the former and miR-124-3p were associated with reduced survival. In vitro miR-139-5p overexpression yielded inconsistent results: while mir-139-5p restoration significantly reduced invasion, the clonogenic capacity of cells was increased. Our study demonstrated that down-regulation of miR-124-3p, miR-139-5p and miR-584-5p are associated with disease progression in EWS and may serve as a risk assessment biomarkers though, as seen for mir-139-5p, their specific role remain to be elucidated for considering tailoring treatment options. (AU)

• 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
• Modalidade de apoio: Auxílio à Pesquisa - Regular