PLK1-associated microRNAs are correlated with pediatric medulloblastoma prognosis

Author(s)

Pezuk, Julia Alejandra ; Brassesco, Maria Sol ; de Oliveira, Ricardo Santos ; Machado, Helio Rubens ; Neder, Luciano ; Scrideli, Carlos Alberto ; Tone, Luiz Gonzaga

• Document type: Journal article
• Source: CHILD'S NERVOUS SYSTEM; v. 33, n. 4, p. 609-615, APR 2017.
• Web of Science Citations: 7

Abstract

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)

• FAPESP's process: 11/11287-3 - Studies of potential therapeutic targets and biological pathways involved in medulloblastoma
• Grantee: Luiz Gonzaga Tone
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/01026-8 - POLO-LIKE KINASE IN MEDULLOBLASTOMA: PLKs genes expression evaluation and in vitro effects of pharmacological inhibition of PLK1.
• Grantee: Julia Alejandra Pezuk
• Support Opportunities: Scholarships in Brazil - Doctorate