Project description:In order to improve the understanding of the impact of sex during colorectal cancer development we sequenced, for the first time, the colonic epithelium of wild-type mice of both sexes treated with 9 or 15 weeks AOM/DSS.
Project description:To find out which miRNAs are significantly differential expression and potentially involved in the process of inflammation promoting carcinogenesis of colorectal cancer (CRC). We established a colitis-associated CRC (AOM/DSS, Azoxymethane/Dextran sulfate sodium salt) model, colitis (DSS) model and high dose carcinogen (AOM, about 5 times AOM amount given than AOM/DSS model) model. At day 100 when tumor formed in AOM/DSS bearing mice (colitis-associated CRC mice) but no tumor was found in AOM (high dose carcinogen) and DSS model, we employed miRNA microarray as a discovery platform to identify genes with the potential to involve in the progression of CRC promoted by inflammation. 5-7 weeks female BALB/c mice, (1) AOM/DSS group: AOM 12.5mg/kg i.p. at day 1, DSS drinking 5d/21dx3circles from day 5; (2) AOM group: AOM 10mg/kg i.p. 1/weekx6 from day 1; (3) DSS group: DSS drinking 5d/21dx3circles from day 5. The distal colon epithelial tissues were collected at day100 when tumor formed in AOM/DSS bearing mice. The miRNA microarray experiments were performed together.
Project description:To find out which mRNAs are significantly differential expression and potentially involved in the process of inflammation promoting carcinogenesis of colorectal cancer (CRC). We established a colitis-associated CRC (AOM/DSS, Azoxymethane/Dextran sulfate sodium salt) model, colitis (DSS) model and high dose carcinogen (AOM, about 5 times AOM amount given than AOM/DSS model) model. At day 100 when tumor formed in AOM/DSS bearing mice (colitis-associated CRC mice) but no tumor was found in AOM (high dose carcinogen) and DSS model, we employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to involve in the progression of CRC promoted by inflammation. 5-7 weeks female BALB/c mice, (1) AOM/DSS group: AOM 12.5mg/kg i.p. at day 1, DSS drinking 5d/21dx3circles from day 5; (2) AOM group: AOM 10mg/kg i.p. 1/weekx6 from day 1; (3) DSS group: DSS drinking 5d/21dx3circles from day 5. The distal colon epithelial tissues were collected at day100 when tumor formed in AOM/DSS bearing mice. The whole genome microarray expression profiling experiments were performed together.
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are using transcriptome profiling (RNA-seq) to evaluate the effects of anti-S100a9 antibody on the global transcriptome of the colon tissues of the AOM/DSS mouse model (a model that mimics the human colitis-associated colon cancer development). Methods: 36 five-week-old male ICR mice were randomized divided into three groups: control (i.e. no AOM/DSS and antibody treatment), AOM/DSS+IgG Ab (1.5 mg/kg), and AOM/DSS+anti-S100a9 Ab (1.5 mg/kg). Mice were intraperitoneal injected with a single dose of 10 mg/kg azoxymethane (AOM) (A5486; Sigma) on day 1. One week after the AOM injection, mice were given three cycles of DSS (cycle 1: 2%, 7 days; cycle 2: 1.5%, 5 days; and cycle 3: 1.5%, 5 days, DSS: 36–50 kDa; MP Biomedicals, CA, USA) in their drinking water, and then distilled water until the end of the experiment. Antibodies were administrated intravenously every two days during the three cycles of DSS treatment. Mice were sequentially killed randomly at the end of the 18th week, and at least five mice were killed for each group at each time point. RNAs were extracted by Trizol and sequenced by Solexa high-throughput sequencing service (Oebiotech, Shanghai, China). Data were extracted and normalized according to the manufacturer’s standard protocol.Each group has three mices' colon tissues be tested. Results: Log-fold changes of up- or down-regulated mRNAs between the control and experiment group were selected with a significance threshold of p<0.05. There are 1017 mRNAs were up-regulated and 815 were down-regulated in “AOM/DSS+IgG Ab" group comparing to “control" group. There are 385 mRNAs were up-regulated and 163 were down-regulated in “AOM/DSS+anti-S100a9 Ab" group comparing to “control" group. There are 1314 mRNAs were up-regulated and 968 were down-regulated in “AOM/DSS+anti-S100a9 Ab" group comparing to “AOM/DSS+IgG Ab". Conclusions: Our study describes the global transciptome changes of colon tissues of the AOM/DSS mouse model induced by anti-S100a9 antibody treatment.
Project description:To find out which miRNAs are significantly differential expression and potentially involved in the process of inflammation promoting carcinogenesis of colorectal cancer (CRC). We established a colitis-associated CRC (AOM/DSS, Azoxymethane/Dextran sulfate sodium salt) model, colitis (DSS) model and high dose carcinogen (AOM, about 5 times AOM amount given than AOM/DSS model) model. At day 100 when tumor formed in AOM/DSS bearing mice (colitis-associated CRC mice) but no tumor was found in AOM (high dose carcinogen) and DSS model, we employed miRNA microarray as a discovery platform to identify genes with the potential to involve in the progression of CRC promoted by inflammation.
Project description:To find out which mRNAs are significantly differential expression and potentially involved in the process of inflammation promoting carcinogenesis of colorectal cancer (CRC). We established a colitis-associated CRC (AOM/DSS, Azoxymethane/Dextran sulfate sodium salt) model, colitis (DSS) model and high dose carcinogen (AOM, about 5 times AOM amount given than AOM/DSS model) model. At day 100 when tumor formed in AOM/DSS bearing mice (colitis-associated CRC mice) but no tumor was found in AOM (high dose carcinogen) and DSS model, we employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to involve in the progression of CRC promoted by inflammation.
Project description:The purpose of this study was to determine which genes are differentially regulated by the Ras-related small GTPase RBJ after induction by AOM/DSS treatment in the colon of C57BL/6 mice compared to RBJ+/+ mice. The results demonstrate decreased induction of cell proliferation-associated genes in RBJ-/- mice than in RBJ+/+ mice on day 80 after AOM/DSS treatment. The majority of differentially expressed genes are regulated by MEK/ERK signaling pathway. Thus RBJ may be involved in the regulation of tumor progression and tumorigenesis.
Project description:In humans with UC, low-grade dysplasia also develops predominantly in the distal colon, progresses more rapidly to neoplasia than proximal colon low-grade dysplasia and associates with worse patient prognosis. In a mouse model of colitis-associated carcinogenesis induced by administration of the mutagen AOM and the luminal toxin DSS, tumors also develop exclusively in the distal part of the large intestine. We monitored global changes in the transcriptome of mouse proximal and distal colon during exposure to AOM/DSS with the aim to define biological pathways and processes that characterize regional responses of the large intestine to colitis-associated carcinogenesis.
Project description:The objective of the study was to evalute the changes in gene expression associated to UCP2 invalidation in colon tumors from AOM/DSS-treated mice We used microarrays (Mouse Gene 2.0) to investigate gene expression in Ucp2+/+ and Ucp2-/- colon tumors
Project description:Genome-wide methylation analysis was performed by methylated DNA immunoprecipitation (MeDIP)-CpG island (CGI) microarray analysis to identify candidate CGIs specifically methylated in mouse colon tumors associated with colitis. We sucessfully identified 23 candidate CGIs methylated in tumors. Two samples were analyzed by MeDIP-CGI microarray. One is a pool of two AOM/DSS-induced colon tumors in BALB/c mice and another is a pool of two normal colonic epithelial cell samples obtained from untreated BALB/c mice by the crypt isolation technique. The pool of normal colonic epithelial cell samples was used as reference. Dye-swaps were not perfromed. The methylation statuses of CGIs identified by microarray were confirmed by another method, methylation-specific PCR.