title: Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral cancer cells.
abstract: BACKGROUND
  The human dicer1 gene has been predicted to produce several mRNA variants that encode truncated Dicer1 proteins of varying lengths. One of these Dicer1 variants, Dicer1e, was recently found to be differentially expressed in breast cancer cells. Because the expression and function of the Dicer1e protein variant has not been well characterized and the underlying molecular mechanisms for the development of oral squamous cell carcinomas (OSCCs) are poorly understood, the present study sought to characterize the biological role of Dicer1e and determine its relationship, if any, to OSCC pathogenesis.
  
  
  METHODS
  Western blot analyses were used to examine Dicer1e expression levels in a panel of oral cancer cells/tissues and during epithelial-mesenchymal transition (EMT), followed by 5'/3'-RACE analyses to obtain the full-length Dicer1e transcript. Biochemical fractionation and indirect immunofluorescent studies were performed to determine the cellular localization of Dicer1e and the effects of Dicer1e silencing on cancer cell proliferation, clonogenicity, and drug sensitivity were also assessed.
  
  
  RESULTS
  Dicer1e protein levels were found to be overexpressed in OSCC cell lines of epithelial phenotype and in OSCC tissues with its levels downregulated during EMT. Moreover, the Dicer1e protein was observed to predominantly localize in the nucleus. 5'/3'-RACE analyses confirmed the presence of the Dicer1e transcript and silencing of Dicer1e impaired both cancer cell proliferation and clonogenicity by inducing either apoptosis and/or G2/M cell cycle arrest. Lastly, Dicer1e knockdown enhanced the chemosensitivity of oral cancer cells to cisplatin.
  
  
  CONCLUSIONS
  The expression levels of Dicer1e influence the pathogenesis of oral cancer cells and alter their response to chemosensitivity, thus supporting the importance of Dicer1e as a therapeutic target for OSCCs.
authors.forename: Liliana P
authors.initials: LP
authors.lastname: Cantini
authors.forename: Lourdes M
authors.initials: LM
authors.lastname: Andino
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Attaway
authors.forename: Betsy
authors.initials: B
authors.lastname: Butler
authors.forename: Anca
authors.initials: A
authors.lastname: Dumitriu
authors.forename: Aaron
authors.initials: A
authors.lastname: Blackshaw
authors.affiliation: Department of Oral Health Sciences and Center for Oral Health Research, Hollings Cancer Center, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA. jakymiw@musc.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jakymiw
mesh_terms: D017398:Alternative Splicing; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D002945:Cisplatin