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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma

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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]
Total Authors: 7
[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
Total Affiliations: 6
Document type: Journal article
Source: Pathology & Oncology Research; v. 25, n. 1, p. 11-20, JAN 2019.
Web of Science Citations: 2

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)

FAPESP's process: 14/07117-3 - Evaluation of the expression of microRNAs associated with ROCK kinases and their role in the invasion process in osteosarcoma
Grantee:Lara Elis Alberici Delsin
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 14/03877-3 - Evaluation of rock kinases and their interaction with microRNAs in bone sarcomas of childhood: implications for tumor progression and invasion
Grantee:María Sol Brassesco Annichini
Support Opportunities: Regular Research Grants