title: Small RNAs in metastatic and non-metastatic oral squamous cell carcinoma.
abstract: BACKGROUND
  Small non-coding regulatory RNAs control cellular functions at the transcriptional and post-transcriptional levels. Oral squamous cell carcinoma is among the leading cancers in the world and the presence of cervical lymph node metastases is currently its strongest prognostic factor. In this work we aimed at finding small RNAs expressed in oral squamous cell carcinoma that could be associated with the presence of lymph node metastasis.
  
  
  METHODS
  Small RNA libraries from metastatic and non-metastatic oral squamous cell carcinomas were sequenced for the identification and quantification of known small RNAs. Selected markers were validated in plasma samples. Additionally, we used in silico analysis to investigate possible new molecules, not previously described, involved in the metastatic process.
  
  
  RESULTS
  Global expression patterns were not associated with cervical metastases. MiR-21, miR-203 and miR-205 were highly expressed throughout samples, in agreement with their role in epithelial cell biology, but disagreeing with studies correlating these molecules with cancer invasion. Eighteen microRNAs, but no other small RNA class, varied consistently between metastatic and non-metastatic samples. Nine of these microRNAs had been previously detected in human plasma, eight of which presented consistent results between tissue and plasma samples. MiR-31 and miR-130b, known to inhibit several steps in the metastatic process, were over-expressed in non-metastatic samples and the expression of miR-130b was confirmed in plasma of patients showing no metastasis. MiR-181 and miR-296 were detected in metastatic tumors and the expression of miR-296 was confirmed in plasma of patients presenting metastasis. A novel microRNA-like molecule was also associated with non-metastatic samples, potentially targeting cell-signaling mechanisms.
  
  
  CONCLUSIONS
  We corroborate literature data on the role of small RNAs in cancer metastasis and suggest the detection of microRNAs as a tool that may assist in the evaluation of oral squamous cell carcinoma metastatic potential.
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil. patricia.severino@einstein.br.
authors.forename: Patricia
authors.initials: P
authors.lastname: Severino
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil. liliane.oliveira@einstein.br.
authors.forename: Liliane Santana
authors.initials: LS
authors.lastname: Oliveira
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil. flavia.andreghetto@einstein.br.
authors.forename: Flávia Maziero
authors.initials: FM
authors.lastname: Andreghetto
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, SP, Brazil. natalia.torres@einstein.br.
authors.forename: Natalia
authors.initials: N
authors.lastname: Torres
authors.affiliation: Hospital Heliopolis, Departamento de Cirurgia e Otorrinolaringologia, Sao Paulo, SP, Brazil. curioni@usp.br.
authors.forename: Otávio
authors.initials: O
authors.lastname: Curioni
authors.affiliation: Faculdade Ceres, Sao Jose do Rio Preto, SP, Brazil. pmcury@hotmail.com.
authors.forename: Patricia Maluf
authors.initials: PM
authors.lastname: Cury
authors.affiliation: Departamento de Epidemiologia, Faculdade de Saúde Pública, University of Sao Paulo, Sao Paulo, SP, Brazil. toporcov@usp.br.
authors.forename: Tatiana Natasha
authors.initials: TN
authors.lastname: Toporcov
authors.affiliation: Federal University of Technology, Parana, Brazil. paschoal@utfpr.edu.br.
authors.forename: Alexandre Rossi
authors.initials: AR
authors.lastname: Paschoal
authors.affiliation: Instituto de Matemática e Estatística, University of Sao Paulo, Sao Paulo, SP, Brazil. aland@usp.br.
authors.forename: Alan Mitchell
authors.initials: AM
authors.lastname: Durham
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D009367:Neoplasm Staging; D017423:Sequence Analysis, RNA
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs