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Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

miRNAs have been identified as key regulators of almost all cellular processes, therefore, their dysregulation is involved with several diseases, including cancer. miRNAs specifically related to the metastastic cascade are called metastamiRs and can be involved with different steps of this process, including loss of adhesion. Osteosarcoma (OS) is the most common primary malignant pediatric bone tumor that often presents metastatic disease at diagnosis; therefore, a deeper study of adhesion-associated miRNAs could shed light on its pathophysiology. Online databases were used to select four miRNAs (miR-139; miR-181b; miR-584; miR-708) predicted or validated to target proteins related to adherent junctions and focal adhesion pathways, and their expression levels and possible associations with clinical features evaluated in primary OS samples. Our results showed downregulation of miR-139-5p and miR-708-5p in OS samples compared to non-neoplastic controls. Moreover, lower expression of miR-708-5p was associated with poor overall survival and higher expression of miR-181b-5p related to worst chemotherapy response (low HUVOS level). Based on these results, we selected miR-139-5p and miR-708-5p for further functional testing. Inducing the expression of miR-139-5p diminished the clonogenic capacity of the HOS cell line, while upregulation of miR-708-5p was related to a lower cellular adhesion. In summary, this work identified new signatures of microRNA dysregulation that may serve as useful prognostic markers in this aggressive pediatric bone tumor.

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Authors and Affiliations

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

    L. E. A. Delsin

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

    G. M. Roberto

  3. Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System, University of São Paulo, São Paulo, Brazil

    E. E. Engel

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

    P. F. Fedatto, C. A. Scrideli & L. G. Tone

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

    M. S. Brassesco

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

    M. S. Brassesco

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  1. L. E. A. Delsin
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  5. C. A. Scrideli
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  6. L. G. Tone
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  7. M. S. Brassesco
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Correspondence to M. S. Brassesco.

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FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo): Grant 2014/03877-3 and LEAD fellowship 2014/07117-3.

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Delsin, L.E.A., Roberto, G.M., Fedatto, P.F. et al. Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma. Pathol. Oncol. Res. 25, 11–20 (2019). https://doi.org/10.1007/s12253-017-0316-1

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