title: Up-regulated Dicer expression in patients with cutaneous melanoma.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are small non-coding RNAs (18-24 nucleotides) that have recently been shown to regulate gene expression during cancer progression. Dicer, a central enzyme in the multi-component miRNA biogenesis pathway, is involved in cutting precursor miRNAs to functionally mature forms. Emerging evidence shows that Dicer expression is deregulated in some human malignancies and it correlates with tumor progression, yet this role has not yet been investigated in skin cancers.
  
  
  RESULTS
  Using an anti-human monoclonal antibody against Dicer and immunohistochemistry, we compared the expression of Dicer protein among 404 clinically annotated controls and skin tumors consisting of melanocytic nevi (n = 71), a variety of melanomas (n = 223), carcinomas (n = 73) and sarcomas (n = 12). Results showed a cell-specific up-regulated Dicer in 81% of cutaneous, 80% of acrolentiginous and 96% of metastatic melanoma specimens compared to carcinoma or sarcoma specimens (P<0.0001). The expression of Dicer was significantly higher in melanomas compared to benign melanocytic nevi (P<0.0001). In patients with cutaneous melanomas, Dicer up-regulation was found to be significantly associated with an increased tumor mitotic index (P = 0.04), Breslow's depth of invasion (P = 0.03), nodal metastasis (P = 0.04) and a higher American Joint Committee on Caner (AJCC) clinical stage (P = 0.009). Using western blot analysis, we confirmed the cell-specific up-regulation of Dicer protein in vitro. A pooled-analysis on mRNA profiling in cutaneous tumors showed up-regulation of Dicer at the RNA level in cutaneous melanoma, also showing deregulation of other enzymes that participate in the biogenesis and maturation of canonical miRNAs.
  
  
  CONCLUSIONS
  Increased Dicer expression may be a clinically useful biomarker for patients with cutaneous melanoma. Understanding deregulation of Dicer and its influence on miRNA maturation is needed to predict the susceptibility of melanoma patients to miRNA-based therapy in the future.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Ma
authors.forename: Helen
authors.initials: H
authors.lastname: Swede
authors.forename: David
authors.initials: D
authors.lastname: Cassarino
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fleming
authors.forename: Andrew
authors.initials: A
authors.lastname: Fire
authors.forename: Soheil S
authors.initials: SS
authors.lastname: Dadras
mesh_terms: D002460:Cell Line; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D043244:Ribonuclease III