Changes of expression of miR-155 in colitis-associated colonic carcinogenesis.

Weiwei LI; Wenxiao Han; Xinhua Zhao; Hongying Wang

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Changes of expression of miR-155 in colitis-associated colonic carcinogenesis.

Author: Weiwei LI ¹ ; Wenxiao HAN ¹ ; Xinhua ZHAO ¹ ; Hongying WANG ²
Author Information

1. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
2. 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.
Publication Type:Journal Article
MeSH: Adenocarcinoma; chemically induced; genetics; metabolism; Animals; Azoxymethane; toxicity; Carcinogens; toxicity; Cocarcinogenesis; Colitis; chemically induced; genetics; metabolism; Colon; metabolism; Colonic Neoplasms; chemically induced; genetics; metabolism; Dextran Sulfate; toxicity; Gene Expression Profiling; Male; Mice; Mice, Inbred C57BL; MicroRNAs; metabolism; Precancerous Conditions; chemically induced; genetics; metabolism; Up-Regulation
From: Chinese Journal of Oncology 2014;36(4):257-262
CountryChina
Language:Chinese
Abstract:
OBJECTIVETo investigate the changes of miR-155 and its target genes in colitis-associated carcinogenesis.
METHODSColitis-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.
RESULTSColitis-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.
CONCLUSIONThe up-regulation of miR-155 is related to colitis-associated carcinogenesis, but is irrelevant to chronic inflammation in the mouse model.