title: miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation.
abstract: OBJECTIVE
  Renal cell carcinoma is the most common neoplasm of the adult kidney. Currently to our knowledge there are no biomarkers for diagnostic, prognostic or predictive applications for renal cell carcinoma. miRNAs are nonprotein coding RNAs that negatively regulate gene expression and are potential biomarkers for cancer.
  
  
  METHODS
  We analyzed 70 matched pairs of clear cell renal cell carcinoma and normal kidney tissues from the same patients by microarray analysis and validated our results by quantitative real-time polymerase chain reaction. We also performed extensive bioinformatic analysis to explore the role and regulation of miRNAs in clear cell renal cell carcinoma.
  
  
  RESULTS
  We identified 166 miRNAs that were significantly dysregulated in clear cell renal cell carcinoma, including miR-122, miR-155 and miR-210, which had the highest over expression, and miR-200c, miR-335 and miR-218, which were most down-regulated. Analysis of previously reported miRNAs dysregulated in RCC showed overall agreement in the direction of dysregulation. Extensive target prediction analysis revealed that many miRNAs were predicted to target genes involved in renal cell carcinoma pathogenesis. In renal cell carcinoma miRNA dysregulation can be attributed in part to chromosomal aberrations, co-regulation of miRNA clusters and co-expression with host genes. We also performed a preliminary analysis showing that miR-155 expression correlated with clear cell renal cell carcinoma size. This finding must be validated in a larger independent cohort.
  
  
  CONCLUSIONS
  Analysis showed that miRNAs are dysregulated in clear cell renal cell carcinoma and may contribute to kidney cancer pathogenesis by targeting more than 1 key molecule. We identified mechanisms that may contribute to miRNA dysregulation in clear cell renal cell carcinoma. Dysregulated miRNAs represent potential biomarkers for kidney cancer.
authors.affiliation: Department of Laboratory Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: White
authors.forename: Tian Tian
authors.initials: TT
authors.lastname: Bao
authors.forename: Jörg
authors.initials: J
authors.lastname: Grigull
authors.forename: Youssef M
authors.initials: YM
authors.lastname: Youssef
authors.forename: Andrew
authors.initials: A
authors.lastname: Girgis
authors.forename: Maria
authors.initials: M
authors.lastname: Diamandis
authors.forename: Eman
authors.initials: E
authors.lastname: Fatoohi
authors.forename: Maged
authors.initials: M
authors.lastname: Metias
authors.forename: R John
authors.initials: RJ
authors.lastname: Honey
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Pace
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs