title: PLK1-associated microRNAs are correlated with pediatric medulloblastoma prognosis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. julia.pezuk@hotmail.com.|Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil. julia.pezuk@hotmail.com.
authors.forename: Julia Alejandra
authors.initials: JA
authors.lastname: Pezuk
authors.affiliation: Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: María Sol
authors.initials: MS
authors.lastname: Brassesco
authors.affiliation: Department of Surgery and Anatomy, University of São Paulo, São Paulo, Brazil.
authors.forename: Ricardo Santos
authors.initials: RS
authors.lastname: de Oliveira
authors.affiliation: Department of Surgery and Anatomy, University of São Paulo, São Paulo, Brazil.
authors.forename: Hélio Rubens
authors.initials: HR
authors.lastname: Machado
authors.affiliation: Department of Pathology, University of São Paulo, São Paulo, Brazil.
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Scrideli
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Luiz Gonzaga
authors.initials: LG
authors.lastname: Tone
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1
keywords: Medulloblastoma; PLKs; miR-100; miR-126; miR-217; miR-593*