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microRNA-138-5p as a Worse Prognosis Biomarker in Pediatric, Adolescent, and Young Adult Osteosarcoma

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Pathology & Oncology Research

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor with two peaks of incidence, in early adolescence and the elderly. Patients affected with this malignancy often present metastatic disease at diagnosis, and despite multimodality therapy, survival has not improved substantially over the past 3 decades. Recently, miR-138-5p, proposed as a crucial intracellular mediator of invasion, has been recognized to target the Rho-associated coiled-coil containing protein kinase 2 (ROCK2). Dysregulation of ROCK1 and ROCK2 was also described in OS, being associated to higher metastasis incidence and worse prognosis. Nonetheless, the specific roles of miR-138-5p in pediatric and young adult OS and its ability to modulate these kinases remain to be established. Thus, in the present study, the expression levels miR-138-5p were evaluated in a consecutive cohort of exclusively pediatric and young adult primary OS samples. In contrast to previous reports that included adult tissues, our results showed upregulation of miR-138-5p associated with reduced event-free survival and relapsed cases. In parallel, ROCK1 mRNA levels were significantly reduced in tumor samples and negatively correlated with miR-138-5p. Similar correlations were observed after studying the profiles of ROCK1 and ROCK2 by immunohistochemistry. Our data present miR-138-5p as a consistent prognostic factor in pediatric and young adult OS, reinforcing its participation in the post-transcriptional regulation of ROCK kinases.

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Funding

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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Author notes

  1. Gabriela Molinari Roberto and Regia Caroline Lira contributed equally to this work

Authors and Affiliations

  1. Regional Blood Center, University of São Paulo, São Paulo, Brazil

    Gabriela Molinari Roberto

  2. Department of Pediatrics, University of São Paulo, São Paulo, Brazil

    Regia Caroline Lira

  3. Department of Genetics, University of São Paulo, São Paulo, Brazil

    Lara Elis Delsin & Gabriela Maciel Vieira

  4. Department Cell Biology, University of São Paulo, São Paulo, Brazil

    Marcela Oliveira Silva, Carlos Alberto Scrideli & Luiz Gonzaga Tone

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

    Rodrigo Guedes Hakime & María Sol Brassesco

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

    Mauricio Eiji Yamashita & Edgard Eduard Engel

  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. Gabriela Molinari Roberto
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Correspondence to María Sol Brassesco.

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Roberto, G.M., Lira, R.C., Delsin, L.E. et al. microRNA-138-5p as a Worse Prognosis Biomarker in Pediatric, Adolescent, and Young Adult Osteosarcoma. Pathol. Oncol. Res. 26, 877–883 (2020). https://doi.org/10.1007/s12253-019-00633-0

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