Identification of gene expression changes from colitis to CRC in the mouse CAC model.
Identification of gene expression changes from colitis to CRC in the mouse CAC model.
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小鼠 CAC 模型中从结肠炎到 CRC 的基因表达变化的鉴定
DOI：
10.1371/journal.pone.0095347
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li X;Gao Y;Yang M;Zhao Q;Wang G;Yang YM;Yang Y;Liu H;Zhang Y
结直肠癌发生和炎症之间的联系是众所周知的，但潜在的分子机制尚未阐明。化学诱导的结肠炎相关癌症（CAC）是研究炎症和癌症之间联系的杰出小鼠模型。此外，CAC模型用于检查用于临床实践的新的诊断、预后和预测标志物。在此，使用氧化偶氮甲烷（AOM）和葡聚糖硫酸钠盐（DSS）在BALB/c小鼠中在不到100天内建立CAC模型。我们检测了三组小鼠的mRNA表达谱：对照未处理小鼠（K）、DSS诱导的慢性结肠炎小鼠（D）和AOM/DSS诱导的CAC（AD）小鼠。我们在三组中鉴定了6301个差异表达基因（DEG），包括93个持续上调的基因和139个持续下调的基因。基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径分析显示，最持久的DEG在肿瘤微环境中显著富集代谢或炎症组分。此外，通过蛋白质-蛋白质相互作用（PPI）网络分析，几个相关的DEG被确定为潜在的DEG。我们从DEG和潜在的DEG中选择了14个关键基因进行进一步的定量实时PCR（qPCR）验证。6个持续上调，3个持续下调DEG，其他3个基因的结果与微阵列数据一致。我们证明了12个关键基因的调控，这些基因在结肠炎相关的结直肠癌中特异性参与Wnt信号传导、细胞因子和细胞因子受体相互作用、稳态和肿瘤相关代谢。我们的研究结果表明，肿瘤微环境的代谢和炎症介质之间的密切关系是目前在CAC。
A connection between colorectal carcinogenesis and inflammation is well known, but the underlying molecular mechanisms have not been elucidated. Chemically induced colitis-associated cancer (CAC) is an outstanding mouse model for studying the link between inflammation and cancer. Additionally, the CAC model is used for examining novel diagnostic, prognostic, and predictive markers for use in clinical practice. Here, a CAC model was established in less than 100 days using azoxymethane (AOM) with dextran sulfate sodium salt (DSS) in BALB/c mice. We examined the mRNA expression profiles of three groups: control untreated mice (K), DSS-induced chronic colitis mice (D), and AOM/DSS-induced CAC (AD) mice. We identified 6301 differentially expressed genes (DEGs) among the three groups, including 93 persistently upregulated genes and 139 persistently downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the most persistent DEGs were significantly enriched in metabolic or inflammatory components in the tumor microenvironment. Furthermore, several associated DEGs were identified as potential DEGs by protein-protein interaction (PPI) network analysis. We selected 14 key genes from the DEGs and potential DEGs for further quantitative real-time PCR (qPCR) verification. Six persistently upregulated, 3 persistently downregulated DEGs, and the other 3 genes showed results consistent with the microarray data. We demonstrated the regulation of 12 key genes specifically involved in Wnt signaling, cytokine and cytokine receptor interactions, homeostasis, and tumor-associated metabolism during colitis-associated CRC. Our results suggest that a close relationship between metabolic and inflammatory mediators of the tumor microenvironment is present in CAC.
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影响因子：
24.5
作者：
Lutgens, M. W. M. D.;Vleggaar, F. P.;Samsom, M.
通讯作者：
Samsom, M.
影响因子：
5.8
作者：
Pagel, P;Kovac, S;Frishman, D
通讯作者：
Frishman, D
影响因子：
7
作者：
Makawita, Shalini;Smith, Chris;Diamandis, Eleftherios P.
通讯作者：
Diamandis, Eleftherios P.
通过文献挖掘与多种相互作用证据来源相结合的小鼠蛋白质相互作用组
影响因子：
3.5
作者：
Li, Xiao;Cai, Haoyang;Zhang, Yizheng
通讯作者：
Zhang, Yizheng
影响因子：
120.7
作者：
Burke, W;Petersen, G;Varricchio, C
通讯作者：
Varricchio, C