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

Pathology oncology research: POR

article

Roberto, Gabriela Molinari¹  Tone, Luiz Gonzaga²  Brassesco, María Sol³  Lira, Regia Caroline⁵  Delsin, Lara Elis⁶  Vieira, Gabriela Maciel⁶  Silva, Marcela Oliveira²  Hakime, Rodrigo Guedes³  Yamashita, Mauricio Eiji⁷  Engel, Edgard Eduard⁷  Scrideli, Carlos Alberto² 

[1] Regional Blood Center, University of São Paulo;Department Cell Biology, University of São Paulo;Department of Biomechanics, Medicine and Rehabilitation of the Locomotor System of Ribeirão Preto Medical School, University of São Paulo;Departamento de Biologia;Department of Pediatrics, University of São Paulo;Department of Genetics, University of São Paulo;Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo

关键词: miR-138;    ROCK;    microRNA;    Osteosarcoma;    Prognosis;   

DOI  :  10.1007/s12253-019-00633-0

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown