title: Differential expression of microRNAs in tumors from chronically inflamed or genetic (APC(Min/+)) models of colon cancer.
abstract: BACKGROUND
  Chronic inflammation associated with ulcerative colitis predisposes individuals to increased colon cancer risk. The aim of these studies was to identify microRNAs that are aberrantly regulated during inflammation and may participate in transformation of colonic epithelial cells in the inflammatory setting.
  
  
  RESULTS
  We have use quantitative PCR arrays to compare microRNA (miRNA) expression in tumors and control colonic epithelial cells isolated from distal colons of chronically inflamed mice and APC(Min/+) mice. Rank order statistics was utilized to identify differentially regulated miRNAs in tumors that arose due to chronic inflammation and/or to germline APC mutation. Eight high priority miRNAs were identified: miR-215, miR-137, miR-708, miR-31, and miR-135b were differentially expressed in APC tumors and miR-215, miR-133a, miR-467d, miR-218, miR-708, miR-31, and miR-135b in colitis-associated tumors. Four of these (miR-215, miR-708, miR-31, and miR-135b) were common to both tumors types, and dysregulation of these miRNAs was confirmed in an independent sample set. Target prediction and pathway analysis suggests that these microRNAs, in the aggregate, regulate signaling pathways related to MAPK, PI3K, WNT, and TGF-β, all of which are known to be involved in transformation.
  
  
  CONCLUSIONS
  We conclude that these four miRNAs are dysregulated at some very early stage in transformation of colonic epithelial cells. This response is not dependent on the mechanism of initiation of transformation (inflammation versus germline mutation), suggesting that the miRNAs that we have identified are likely to regulate critical signaling pathways that are central to early events in transformation of colonic epithelial cells.
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida, United States of America.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Necela
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Carr
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000235:genetics*; D003110:Colonic Neoplasms / Q000150:complications / Q000235:genetics*; D005260:Female; D017491:Genes, APC; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs