title: Lymph node or perineural invasion is associated with low miR-15a, miR-34c and miR-199b levels in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  MicroRNAs (miRNAs or miRs) are post-transcriptional regulators of eukaryotic cells and knowledge of differences in miR levels may provide new approaches to diagnosis and therapy.
  
  
  METHODS
  The present study measured the levels of nine miRs in head and neck squamous cell carcinomas (HNSCC) and determined whether clinical pathological features are associated with differences in miR levels. SET (I2PP2A) and PTEN protein levels were also measured, since their levels can be regulated by miR-199b and miR-21, respectively. Nine miRs (miR-15a, miR-21, miR-29b, miR-34c, miR-100, miR-125b, miR-137, miR-133b and miR-199b) were measured by real time qRT-PCR in HNSCC samples from 32 patients and eight resection margins. SET (I2PP2A) and PTEN protein levels were estimated by immunohistochemistry in paired HNSCC tissues and their matched resection margins.
  
  
  RESULTS
  In HNSCC, the presence of lymph node invasion was associated with low miR-15a, miR-34c and miR-199b levels, whereas the presence of perineural invasion was associated with low miR-199b levels. In addition, miR-21 levels were high whereas miR-100 and miR-125b levels were low in HNSCC compared to the resection margins. When HNSCC line HN12, with or without knockdown of SET, were transfected with miR-34c inhibitor or miR-34c mimic, the miR-34c inhibitor increased cell invasion capacity while miR-34c mimic decreased the cell invasion.
  
  
  CONCLUSIONS
  We showed that the levels of specific miRs in tumor tissue can provide insight into the maintenance and progression of HNSCC.
  
  
  CONCLUSIONS
  MiRNAs are up- or down-regulated during cancer development and progression; they can be prognosis markers and therapeutic targets in HNSCC.
authors.affiliation: Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Brazil; Hemotherapy Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Lucas O
authors.initials: LO
authors.lastname: Sousa
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Lays M
authors.initials: LM
authors.lastname: Sobral
authors.affiliation: Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Camila S
authors.initials: CS
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Fabiano P
authors.initials: FP
authors.lastname: Saggioro
authors.affiliation: Cancer Institute of the State of São Paulo (ICESP), São Paulo, Brazil.
authors.forename: Rossana V M
authors.initials: RV
authors.lastname: López
authors.affiliation: Hemotherapy Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Panepucci
authors.affiliation: Department of Chemistry and Physics, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Curti
authors.affiliation: Hemotherapy Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
authors.affiliation: Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Brazil; Hemotherapy Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Greene
authors.affiliation: Hemotherapy Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Brazil; Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Andréia M
authors.initials: AM
authors.lastname: Leopoldino
keywords: Lymph node invasion; Perineural invasion; miR-15a; miR-199b; miR-34c