Association of aberrant DNA methylation in Apc(min/+) mice with the epithelial-mesenchymal transition and Wnt/β-catenin pathways: genome-wide analysis using MeDIP-seq.
Association of aberrant DNA methylation in Apc(min/+) mice with the epithelial-mesenchymal transition and Wnt/β-catenin pathways: genome-wide analysis using MeDIP-seq.
复制标题
DOI：
10.1186/s13578-015-0013-2
复制
发表时间：
2015
影响因子：
7.5
通讯作者：
Kong AN
中科院分区：
文献类型：
--
作者：
Guo Y;Lee JH;Shu L;Huang Y;Li W;Zhang C;Yang AY;Boyanapalli SS;Perekatt A;Hart RP;Verzi M;Kong AN
CpG二核苷酸胞嘧啶残基上5位碳（5 mC）的异常DNA甲基化可能是结肠癌中最广泛表征的表观遗传修饰。已经表明，腺瘤性结肠息肉病（APC）功能的丧失启动肿瘤发生，并且另外的遗传和表观遗传事件参与结肠癌进展。我们的目的是研究Apcmin/+小鼠肠道肿瘤发生的全基因组DNA甲基化谱。使用甲基化DNA免疫沉淀（MeDIP），然后进行下一代测序，以确定Apcmin/+小鼠中DNA甲基化变化的总体特征。从来自Apcmin/+小鼠的腺瘤性息肉和来自年龄匹配的Apc+/+同窝仔的正常肠组织中提取DNA，并进行MeDIP-seq测定。使用不相容性途径分析（IPA）软件分析基因相互作用的数据。在Apcmin/+小鼠中，共有17，265个差异甲基化区域（DMR）显示甲基化变化≥ 2倍（log 2）;在这些DMR中，分别有9，078个（52.6%）和8，187个（47.4%）显示甲基化升高和降低。甲基化模式改变的基因主要定位于与癌症和胃肠道疾病相关的网络和生物功能。在这些网络中，几个典型的途径，如上皮-间质转化（EMT）和Wnt/β-连环蛋白途径，与Apcmin/+小鼠息肉的全基因组甲基化变化显著相关。EMT和Wnt/β-连环蛋白通路中某些差异甲基化分子的鉴定，如APC 2（结肠腺瘤性息肉病2）、SFRP 2（分泌型卷曲相关蛋白2）和DKK 3（dickkopf相关蛋白3），与之前的出版物一致。我们的研究结果表明，Apcmin/+小鼠表现出广泛的异常DNA甲基化，影响某些信号通路，如EMT和Wnt/β-catenin通路。Apcmin/+小鼠的全基因组DNA甲基化谱为未来研究结肠肿瘤发生中的表观遗传基因调控和结肠癌预防提供了信息。
Aberrant DNA methylation at the 5-carbon on cytosine residues (5mC) in CpG dinucleotides is probably the most extensively characterized epigenetic modification in colon cancer. It has been suggested that the loss of adenomatous polyposis coli (APC) function initiates tumorigenesis and that additional genetic and epigenetic events are involved in colon cancer progression. We aimed to study the genome-wide DNA methylation profiles of intestinal tumorigenesis in Apcmin/+ mice. Methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing was used to determine the global profile of DNA methylation changes in Apcmin/+ mice. DNA was extracted from adenomatous polyps from Apcmin/+ mice and from normal intestinal tissue from age-matched Apc+/+ littermates, and the MeDIP-seq assay was performed. Ingenuity Pathway Analysis (IPA) software was used to analyze the data for gene interactions. A total of 17,265 differentially methylated regions (DMRs) displayed a ≥ 2-fold change (log2) in methylation in Apcmin/+ mice; among these DMRs, 9,078 (52.6 %) and 8,187 (47.4 %) exhibited increased and decreased methylation, respectively. Genes with altered methylation patterns were mainly mapped to networks and biological functions associated with cancer and gastrointestinal diseases. Among these networks, several canonical pathways, such as the epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathways, were significantly associated with genome-wide methylation changes in polyps from Apcmin/+ mice. The identification of certain differentially methylated molecules in the EMT and Wnt/β-catenin pathways, such as APC2 (adenomatosis polyposis coli 2), SFRP2 (secreted frizzled-related protein 2), and DKK3 (dickkopf-related protein 3), was consistent with previous publications. Our findings indicated that Apcmin/+ mice exhibited extensive aberrant DNA methylation that affected certain signaling pathways, such as the EMT and Wnt/β-catenin pathways. The genome-wide DNA methylation profile of Apcmin/+ mice is informative for future studies investigating epigenetic gene regulation in colon tumorigenesis and the prevention of colon cancer.
登录
查看更多内容
影响因子：
3.9
作者：
Cieślik M;Hoang SA;Baranova N;Chodaparambil S;Kumar M;Allison DF;Xu X;Wamsley JJ;Gray L;Jones DR;Mayo MW;Bekiranov S
通讯作者：
Bekiranov S
影响因子：
50.3
作者：
De Carvalho DD;Sharma S;You JS;Su SF;Taberlay PC;Kelly TK;Yang X;Liang G;Jones PA
通讯作者：
Jones PA
影响因子：
3.2
作者：
Dhir, Mashaal;Montgomery, Elizabeth A.;Glockner, Sabine C.;Schuebel, Kornel E.;Hooker, Craig M.;Herman, James G.;Baylin, Stephen B.;Gearhart, Susan L.;Ahuja, Nita
通讯作者：
Ahuja, Nita
影响因子：
4.5
作者：
Grimm C;Chavez L;Vilardell M;Farrall AL;Tierling S;Böhm JW;Grote P;Lienhard M;Dietrich J;Timmermann B;Walter J;Schweiger MR;Lehrach H;Herwig R;Herrmann BG;Morkel M
通讯作者：
Morkel M
Twist2通过促进上皮-间质转化和癌症干细胞样细胞自我更新促进乳腺癌进展
影响因子：
8
作者：
Fang, X.;Cai, Y.;Ouyang, G.
通讯作者：
Ouyang, G.