title: Elevated expression of prostate cancer-associated genes is linked to down-regulation of microRNAs.
abstract: BACKGROUND
  Recent evidence suggests that the prostate cancer (PCa)-specific up-regulation of certain genes such as AMACR, EZH2, PSGR, PSMA and TRPM8 could be associated with an aberrant expression of non-coding microRNAs (miRNA).
  
  
  METHODS
  In silico analyses were used to search for miRNAs being putative regulators of PCa-associated genes. The expression of nine selected miRNAs (hsa-miR-101, -138, -186, -224, -26a, -26b, -374a, -410, -660) as well as of the aforementioned PCa-associated genes was analyzed by quantitative PCR using 50 malignant (Tu) and matched non-malignant (Tf) tissue samples from prostatectomy specimens as well as 30 samples from patients with benign prostatic hyperplasia (BPH). Then, correlations between paired miRNA and target gene expression levels were analyzed. Furthermore, the effect of exogenously administered miR-26a on selected target genes was determined by quantitative PCR and Western Blot in various PCa cell lines. A luciferase reporter assay was used for target validation.
  
  
  RESULTS
  The expression of all selected miRNAs was decreased in PCa tissue samples compared to either control group (Tu vs Tf: -1.35 to -5.61-fold; Tu vs BPH: -1.17 to -5.49-fold). The down-regulation of most miRNAs inversely correlated with an up-regulation of their putative target genes with Spearman correlation coefficients ranging from -0.107 to -0.551. MiR-186 showed a significantly diminished expression in patients with non-organ confined PCa and initial metastases. Furthermore, over-expression of miR-26a reduced the mRNA and protein expression of its potential target gene AMACR in vitro. Using the luciferase reporter assay AMACR was validated as new target for miR-26a.
  
  
  CONCLUSIONS
  The findings of this study indicate that the expression of specific miRNAs is decreased in PCa and inversely correlates with the up-regulation of their putative target genes. Consequently, miRNAs could contribute to oncogenesis and progression of PCa via an altered miRNA-target gene-interaction.
authors: Department of Urology, University Hospital Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. kati.erdmann@uniklinikum-dresden.de.
authors: Kati
authors: K
authors: Erdmann
authors: Knut
authors: K
authors: Kaulke
authors: Cathleen
authors: C
authors: Thomae
authors: Doreen
authors: D
authors: Huebner
authors: Mildred
authors: M
authors: Sergon
authors: Michael
authors: M
authors: Froehner
authors: Manfred P
authors: MP
authors: Wirth
authors: Susanne
authors: S
authors: Fuessel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003198:Computer Simulation; D030541:Databases, Genetic; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D019998:Racemases and Epimerases; C533096:MIRN186 microRNA, human; C528163:MIRN26 microRNA, human; C108352:alpha-methylacyl-CoA racemase