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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

PLK1-associated microRNAs are correlated with pediatric medulloblastoma prognosis

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Autor(es):
Pezuk, Julia Alejandra ; Brassesco, Maria Sol ; de Oliveira, Ricardo Santos ; Machado, Helio Rubens ; Neder, Luciano ; Scrideli, Carlos Alberto ; Tone, Luiz Gonzaga
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: CHILD'S NERVOUS SYSTEM; v. 33, n. 4, p. 609-615, APR 2017.
Citações Web of Science: 7
Resumo

Purpose Medulloblastoma (MB) is the most common malignant tumor of the central nervous system (CNS) in children. Despite its relative good survival rates, treatment can cause long time sequels and may impair patients' lifespan and quality, making the search for new treatment options still necessary. Polo like kinases (PLKs) constitute a five-member serine/threonine kinases family (PLK 1-5) that regulates different stages during cell cycle. Abnormal PLKs expression has been observed in several cancer types, including MB. As gene regulators, miRNAs have also been described with variable expression in cancer. Methods We evaluated gene expression profiles of all PLK family members and related miRNAs (miR-100, miR-126, miR-219, and miR-593{*}) in MB cell lines and tumor samples. Results RT-qPCR analysis revealed increased levels of PLK1-4 in all cell lines and in most MB samples, while PLK5 was found underexpressed. In parallel, miR-100 was also found upregulated while miR-129, miR-216, and miR593{*} were decreased in MB cell lines. Variable miRNAs expression patterns were observed in MB samples. However, a correlation between miR-100 and PLK4 expression was observed, and associations between miR-100, miR-126, and miR-219 expression and overall and event free survival were also evinced in our cohort. Moreover, despite the lack of association with clinico-pathological features, when comparing primary tumors to those relapsed, we found a consistent decrease on PLK2, miR-219, and miR-598{*} and an increase on miR-100 and miR-126. Conclusion Specific dysregulation on PLKs and associated miRNAs may be important in MB and can be used to predict prognosis. Although miRNAs sequences are fundamental to predict its target, the cell type may also be consider once that mRNA repertoire can define different roles for specific miRNA in a given cell. (AU)

Processo FAPESP: 11/01026-8 - POLO-LIKE quinases em meduloblastoma: avaliação da expressão dos genes PLKs e efeitos in vitro da inibição farmacológica da PLK1
Beneficiário:Julia Alejandra Pezuk
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 11/11287-3 - Estudos de potenciais alvos terapêuticos e vias biológicas envolvidas no meduloblastoma
Beneficiário:Luiz Gonzaga Tone
Linha de fomento: Auxílio à Pesquisa - Regular