Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma

Autor(es)

Delsin, L. E. A. ^[1] ; Roberto, G. M. ^[2] ; Fedatto, P. F. ^[3] ; Engel, E. E. ^[4] ; Scrideli, C. A. ^[3] ; Tone, L. G. ^[3] ; Brassesco, M. S. ^{[5, 6]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Genet, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Reg Blood Ctr, Sao Paulo - Brazil

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

^[4] Univ Sao Paulo, Dept Biomech Med & Rehabil Locomotor Syst, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Dept Biol, Sao Paulo - Brazil

^[6] Univ Sao Paulo, FFCLRP, Dept Biol, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Pathology & Oncology Research; v. 25, n. 1, p. 11-20, JAN 2019.
• Citações Web of Science: 2

Resumo

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. (AU)

• Processo FAPESP: 14/07117-3 - Avaliação de microRNAs associados às quinases ROCK em osteosarcoma e seu papel no processo de invasão celular
• Beneficiário: Lara Elis Alberici Delsin
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• 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