title: Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma.
abstract: BACKGROUND
  F-box and WD repeat domain-containing 7 (FBXW7) is a cell cycle regulatory gene whose protein product ubiquitinates positive cell cycle regulators such as c-Myc, cyclin E, and c-Jun, thereby acting as a tumour-suppressor gene. This study focused on microRNA-223 (miR-223), which is a candidate regulator of FBXW7 mRNA. The aim of this study was to clarify the clinical significance of miR-223 and FBXW7 in oesophageal squamous cell carcinoma (ESCC) patients, and to elucidate the mechanism by which FBXW7 is regulated by miR-223.
  
  
  METHODS
  The expression levels of miR-223 and the expression of FBXW7 protein was examined using 109 resected specimens to determine the clinicopathological significance. We also investigated the role of miR-223 in the regulation of FBXW7 expression in ESCC cell lines in an in vitro analysis.
  
  
  RESULTS
  We found that miR-223 expression was significantly higher in cancerous tissues than in the corresponding normal tissues. There was a significant inverse relationship between the expression levels of miR-223 and FBXW7 protein. Moreover, patients with high miR-223 expression demonstrated a significantly poorer prognosis than those with low expression. On the basis of a series of gain-of-function and loss-of-function studies in vitro, we identified FBXW7 as a functional downstream target of miR-223.
  
  
  CONCLUSIONS
  Our present study indicates that high expression of miR-223 had a significant adverse impact on the survival of ESCC patients through repression of the function of FBXW7.
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors: J
authors: J
authors: Kurashige
authors: M
authors: M
authors: Watanabe
authors: M
authors: M
authors: Iwatsuki
authors: K
authors: K
authors: Kinoshita
authors: S
authors: S
authors: Saito
authors: Y
authors: Y
authors: Hiyoshi
authors: H
authors: H
authors: Kamohara
authors: Y
authors: Y
authors: Baba
authors: K
authors: K
authors: Mimori
authors: H
authors: H
authors: Baba
mesh_terms: D000368:Aged; D001483:Base Sequence; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D044783:F-Box Proteins / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D035683:MicroRNAs; D044767:Ubiquitin-Protein Ligases; C513273:FBXW7 protein, human; C525067:MIR223, human