title: The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer.
abstract: BACKGROUND
  Breast cancer is the most common malignancy in women world-wide. Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; and is associated with a high propensity for metastatic spread. Several studies have identified critical roles for microRNAs in breast cancer, but the role of two critical enzymes involved in microRNA biogenesis, Dicer and Drosha, is not well understood, particularly with respect to metastatic progression in this subtype.
  
  
  METHODS
  We examined the expression of Dicer and Drosha in a series of invasive 35 TNBCs with matched normal adjacent tissues (n = 18) and lymph node metastases (n = 15) using semi-quantitative real time RT-PCR. The relationship of their expression with clinical features including age at diagnosis, lymph node positivity and tumour size was analysed.
  
  
  RESULTS
  We report that Dicer was significantly decreased while Drosha was significantly increased in tumours when compared to normal adjacent tissues. While there was no difference in Drosha expression in lymph node metastases when compared to the primary tumour, Dicer was significantly increased. There was no correlation between the expression of either Dicer or Drosha to age at diagnosis, lymph node positivity and tumour size.
  
  
  CONCLUSIONS
  In conclusion, Dicer and Drosha are dysregulated in TNBC and matched lymph node metastases however, the clinical relevance of this is still not known. The altered expression of Dicer and Drosha may serve as markers for disrupted miRNA biogenesis in TNBC.
authors.affiliation: Centre for Information-Based Medicine, Hunter Medical Research Institute, John Hunter Hospital, New Lambton Heights, NSW 2305, Australia. Kelly.Kiejda@newcastle.edu.au.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Avery-Kiejda
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Braye
authors.forename: John F
authors.initials: JF
authors.lastname: Forbes
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D011379:Prognosis; D043244:Ribonuclease III / Q000096:biosynthesis* / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
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