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PLK1-associated microRNAs are correlated with pediatric medulloblastoma prognosis

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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 miR-593* 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.

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Acknowledgements

We are grateful to Rosane de Paula Queiroz and Veridiana Kiill Suazo for assistance. We also thank to FAPESP for financial support Nos. 2011/01026-8 and 2011/11287-3.

Author information

Author notes

  1. Julia Alejandra Pezuk

    Present address: Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil

Authors and Affiliations

  1. Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil

    Julia Alejandra Pezuk

  2. Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    María Sol Brassesco

  3. Department of Surgery and Anatomy, University of São Paulo, São Paulo, Brazil

    Ricardo Santos de Oliveira & Hélio Rubens Machado

  4. Department of Pathology, University of São Paulo, São Paulo, Brazil

    Luciano Neder

  5. Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil

    Carlos Alberto Scrideli & Luiz Gonzaga Tone

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Correspondence to Julia Alejandra Pezuk.

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Fundacao de Amparo e Pesquisa do Estado de Sao Paulo (FAPESP Nos. 2011/01026-8 and 2011/11287-3).

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The authors declare that they have no conflict of interest.

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Pezuk, J.A., Brassesco, M.S., de Oliveira, R.S. et al. PLK1-associated microRNAs are correlated with pediatric medulloblastoma prognosis. Childs Nerv Syst 33, 609–615 (2017). https://doi.org/10.1007/s00381-017-3366-5

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  • DOI: https://doi.org/10.1007/s00381-017-3366-5

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