title: Integrative analysis in oral squamous cell carcinoma reveals DNA copy number-associated miRNAs dysregulating target genes.
abstract: OBJECTIVE
  To better understand possible mechanisms involved in the dysregulation of gene expression unique to oral squamous cell carcinoma (OSCC) metastasis, the investigators examined the differential expression of microRNAs (miRNAs) in OSCC metastasis and their functional impact on target gene expression.
  
  
  METHODS
  Observational assessment of DNA copy number, miRNA, and RNA expression in primary and metastatic OSCC.
  
  
  METHODS
  University of Washington Medical Center and affiliated hospitals.
  
  
  METHODS
  Tumor samples were taken from patients with primary incident OSCC; cells were laser-capture microdissected from 17 nonmetastatic primary tumors and 20 metastatic lymph nodes.
  
  
  METHODS
  DNA copy number aberrations and gene expression profiles were previously determined using Affymetrix 250K Nsp I SNP arrays and HU133 plus 2.0 expression arrays. miRNAs were interrogated with Exiqon's Ready-to-Use PCR Panels assessing the expression of 368 human miRNAs.
  
  
  RESULTS
  Investigators found 31 miRNAs differentially expressed between metastatic and nonmetastatic samples (false discovery rate <0.4; 26 overexpressed and 5 underexpressed in metastatic samples). Expression of 7 of these miRNAs was significantly associated with their DNA copy numbers, and expressions of 8 of these miRNAs were significantly associated with their target genes. Among these unique miRNAs, miR-140-3p, miR-29c, and miR-29a were differentially expressed in metastasis versus nonmetastatic samples and had a strong positive correlation with their DNA copy numbers and a negative correlation with the expression of their target genes.
  
  
  CONCLUSIONS
  Results suggest that DNA copy number aberration may play a role in the dysregulation of some differentially expressed miRNAs in OSCC metastasis, warranting further investigation.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98115-7744, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Serrano
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fan
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Upton
authors.forename: John R
authors.initials: JR
authors.lastname: Houck
authors.forename: Pawadee
authors.initials: P
authors.lastname: Lohavanichbutr
authors.forename: Michael
authors.initials: M
authors.lastname: Kao
authors.forename: Lue Ping
authors.initials: LP
authors.lastname: Zhao
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.forename: Eduardo
authors.initials: E
authors.lastname: Méndez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics*
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D012334:RNA, Neoplasm