Mthfd1 is a modifier of intestinal carcinogenesis

The metabolic pathways that underlie the association between folate deficiency and increased risk for colorectal cancer (CRC) remain unclear. We have studied the effect of C1THF synthase (encoded by the Mthfd1 gene) and dietary folate and choline on intestinal tumor development in Apcmin/+ mice and azoxymethane (AOM)-induced colon cancer in mice. Mthfd1 deficiency did not alter tumor number or load in Apcmin/+ mice, but did result in a decreased incidence of colon tumors. Conversely, Mthfd1 deficiency increased tumor number 3.5-fold and tumor load 2-fold in AOM-treated mice. Here we tested colons isolated from wildtype and Mthfd1-deficient animals for alterations in gene expression. Keywords: genetic modification RNA was isolated from proximal colons of MTHFD heterozygous and wild-type mice raised on a control diet. Three colon samples were isolated from each genotype to provide biological replication.叶酸缺乏与结直肠癌（colorectal cancer, CRC）风险升高之间关联的潜在代谢通路尚未阐明。本研究针对C1四氢叶酸合酶（C1THF synthase，由Mthfd1基因编码）、膳食叶酸与胆碱对Apcmin/+小鼠肠道肿瘤发生，以及氧化偶氮甲烷（azoxymethane, AOM）诱导的小鼠结肠癌的影响展开了探究。在Apcmin/+小鼠中，Mthfd1基因缺失并未改变肿瘤数量与肿瘤负荷，但可降低结肠肿瘤的发生率。与之相反，在经AOM处理的小鼠中，Mthfd1基因缺失可使肿瘤数量增加3.5倍，肿瘤负荷升高2倍。本研究针对野生型与Mthfd1基因缺失型动物的分离结肠组织，检测其基因表达变化情况。关键词：基因修饰（genetic modification）。本研究从喂食对照饲料的MTHFD杂合子与野生型小鼠的近端结肠组织中分离RNA。每种基因型均分离3份结肠组织样本以实现生物学重复。