title: Prognostic significance of miR-215 in colon cancer.
abstract: BACKGROUND
  We have previously shown that miR-215 suppressed the expression of key targets such as thymidylate synthase (TS), dihydrofolate reductase, and denticleless protein homolog (DTL) in colon cancer. miR-215 is a tumor suppressor candidate due to the upregulation of p53 and p21 by targeting DTL. However, high levels of miR-215 conferred chemoresistance due to cell cycle arrest and reduced cell proliferation by suppressing DTL. In this study, the clinical significance of miR-215 was further investigated as a potential prognostic biomarker in colon cancer patients.
  
  
  METHODS
  Total RNAs were extracted from 34 paired normal and colon (stage II and III) tumor specimens using the Trizol-based approach. The levels of miR-215 and a closely related miR-192 were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) expression analysis. The expression of DTL mRNA and protein were quantified by real time qRT-PCR and immunohistochemistry.
  
  
  RESULTS
  The expression levels of miR-192 (P = .0008) and miR-215 (P < .0001) were significantly decreased in colon tumors compared with normal tissues. DTL was significantly over-expressed and was inversely correlated with miR-215, further suggesting an in vivo physiologic relevance of miR-215 mediated DTL suppression. Kaplan-Meier survival analysis by Cox regression revealed that high levels of miR-215 expression (hazard ratio, 3.516; 95% confidence interval, 1.007-12.28, P = .025) are closely associated with poor patient's overall survival. Furthermore, an elevated expression of a miR-215 target protein DTL was detected in colon cancer tissues whereas no expression was present in normal tissues.
  
  
  CONCLUSIONS
  miR-215 has a unique potential as a prognostic biomarker in stage II and III colon cancer.
authors.affiliation: Department of Pathology, State University of New York at Stony Brook, Stony Brook, NY 11794-8691, USA.
authors.forename: Mihriban
authors.initials: M
authors.lastname: Karaayvaz
authors.forename: Timothy
authors.initials: T
authors.lastname: Pal
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zhang
authors.forename: Penelope
authors.initials: P
authors.lastname: Georgakopoulos
authors.forename: Saira
authors.initials: S
authors.lastname: Mehmood
authors.forename: Stephanie
authors.initials: S
authors.lastname: Burke
authors.forename: Kenneth
authors.initials: K
authors.lastname: Shroyer
authors.forename: Jingfang
authors.initials: J
authors.lastname: Ju
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D013940:Thymidylate Synthase / Q000378:metabolism; D046888:Tissue Array Analysis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: C429530:DTL protein, human; C546783:MIRN192 microRNA, human; C553667:MIRN215 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D044767:Ubiquitin-Protein Ligases