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ROCK1-PredictedmicroRNAs Dysregulation Contributes to Tumor Progression in Ewing Sarcoma

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Pathology & Oncology Research

Abstract

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.

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Acknowledgments

FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo): Grant 2014/03877-3 and LEAD and GMV fellowships, 2014/07117-3 and 2014/07118-0.

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Authors and Affiliations

  1. Regional Blood Center, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil

    G. M. Roberto

  2. Department of Genetics, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil

    L. E. A. Delsin & G. M. Vieira

  3. Department Cell Biology, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil

    M. O. Silva

  4. Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    R. G. Hakime

  5. Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil

    N. F. Gava, E. E. Engel & María Sol Brassesco

  6. Department of Pediatrics, Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil

    C. A. Scrideli & L. G. Tone

  7. Departamento de Biologia, FFCLRP-USP, Av. Bandeirantes, 3900 Bairro Monte Alegre, Ribeirão Preto, SP, CEP 14040-901, Brazil

    María Sol Brassesco

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  1. G. M. Roberto
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  2. L. E. A. Delsin
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  3. G. M. Vieira
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Correspondence to María Sol Brassesco.

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Roberto, G.M., Delsin, L.E.A., Vieira, G.M. et al. ROCK1-PredictedmicroRNAs Dysregulation Contributes to Tumor Progression in Ewing Sarcoma. Pathol. Oncol. Res. 26, 133–139 (2020). https://doi.org/10.1007/s12253-017-0374-4

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  • DOI: https://doi.org/10.1007/s12253-017-0374-4

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