title: [Changes of expression of miR-155 in colitis-associated colonic carcinogenesis].
abstract: OBJECTIVE
  To investigate the changes of miR-155 and its target genes in colitis-associated carcinogenesis.
  
  
  METHODS
  Colitis-associated colon cancer was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Mice of three different stages during the development of colon cancer were obtained, named AD1, AD2 and AD3, respectively. A control group of mice without any treatment and a DSS only group representing chronic inflammation without cancer were set up as well. Colon tissue was collected and expression of miR-155 in the colon tissues was measured by real-time fluorescent quantitative PCR. TargetScan and PicTar were used to predict potential target genes of miR-155, which were then preliminarily screened with our gene expression microarray database of AOM-DSS mouse model. Regular PCR was used to confirm the changes of the expression of these potential target genes in AOM-DSS mouse model.
  
  
  RESULTS
  Colitis-associated colon cancer was effectively induced by azoxymethane and dextran sulfate sodium in C57BL/6 mice. Histological examination revealed that the evolution process was sequentially from normal, mild dysplasia, moderate dysplasia, and severe dysplasia to adenocarcinoma in the AOM-DSS mouse model. The level of miR-155 was gradually elevated with the formation of colitis-associated colon cancer. There was no significant difference between the levels of miR-155 expression in the DSS group (0.005 6 ± 0.003 7) and control group (0.012 0 ± 0.005 1) (P > 0.05), but the level of miR-155 in the AD3 group (0.054 4 ± 0.027 0) was significantly higher than that of the DSS group (0.005 6 ± 0.003 7)(P < 0.01). No significant change of miR-155 expression was found in the DSS only group. The relative expression levels of miR-155 in the control group, DSS only group and AD3 group were 0.012 0 ± 0.005 1, 0.005 6 ± 0.003 7, 0.054 4 ± 0.027 0, respectively. Data analysis with the gene expression microarray showed that Tle4, Kcna1, Itk, Bcorl1, Cacna1c, Rspo2 and Foxo3 were potential target genes of miR-155 in the AOM-DSS mouse model. Changes of Kcna1 and Cacna1c in the AOM-DSS mouse model were validated to be consistent with the changes obtained with the gene expression microarray.
  
  
  CONCLUSIONS
  The up-regulation of miR-155 is related to colitis-associated carcinogenesis, but is irrelevant to chronic inflammation in the mouse model.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Wenxiao
authors.initials: W
authors.lastname: Han
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China. Email: hongyingwang@cicams.ac.cn.
authors.forename: Hongying
authors.initials: H
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D003043:Cocarcinogenesis; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002273:Carcinogens; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016264:Dextran Sulfate; D001397:Azoxymethane