title: The miR-17-92 cluster is over expressed in and has an oncogenic effect on renal cell carcinoma.
abstract: OBJECTIVE
  miRNAs are small, nonprotein coding RNAs that are differentially expressed in many malignancies. We previously identified 80 miRNAs that are dysregulated in clear cell renal cell carcinoma. In this study we validated over expression of the miR-17-92 cluster in clear cell renal cell carcinoma and tested the effect of 2 members of this cluster (miR-17-5p and miR-20a) on tumor proliferation. We also elucidated the role of miRNA in clear cell renal cell carcinoma pathogenesis with bioinformatics.
  
  
  METHODS
  miRNA expression was validated by quantitative reverse transcriptase-polymerase chain reaction. The cell proliferation effect of miR-17-5p and miR-20a was tested in a renal adenocarcinoma cell line model. Multiple in silico analyses were done of dysregulated miRNAs.
  
  
  RESULTS
  We validated miR-71-92 cluster over expression in clear cell renal cell carcinoma by quantitative reverse transcriptase-polymerase chain reaction. Transfection of miR-20a inhibitor significantly decreased cell proliferation in a dose dependent manner. Transfection of miR-17-5p, which is not endogenously expressed in the ACHN cell line, led to increased cell proliferation compared to control values. This effect was suppressed by miR-17-5p inhibitor. Bioinformatics analysis identified 10 clusters of miRNAs dysregulated in clear cell renal cell carcinoma that followed the same expression patterns. We also identified matching patterns between reported chromosomal aberration in clear cell renal cell carcinoma and miRNA dysregulation for 37.5% of the miRNAs. Target prediction analysis was done using multiple algorithms. Many key molecules in clear cell renal cell carcinoma pathogenesis, including HIFs, mTOR, VEGF and VHL, were potential targets for dysregulated miRNAs.
  
  
  CONCLUSIONS
  A significant number of dysregulated proteins in clear cell renal cell carcinoma are potential miRNA targets. Also, many clear cell renal cell carcinoma dysregulated miRNAs are phylogenetically conserved.
authors.affiliation: Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.
authors.forename: Tsz-Fung F
authors.initials: TF
authors.lastname: Chow
authors.forename: Marina
authors.initials: M
authors.lastname: Mankaruos
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Youssef
authors.initials: Y
authors.lastname: Youssef
authors.forename: Andrew
authors.initials: A
authors.lastname: Girgis
authors.forename: Sarah
authors.initials: S
authors.lastname: Mossad
authors.forename: Shereen
authors.initials: S
authors.lastname: Metias
authors.forename: Yostina
authors.initials: Y
authors.lastname: Rofael
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: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*
chemical_list: C524941:MIRN17 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs