Department of Clinical Pharmacy, USC School of Pharmacy, Los Angeles, CA 90033, USA.
Department of Clinical Pharmacy, USC School of Pharmacy, Los Angeles, CA 90033, USA.
J Nutr Biochem. 2019 Jul;69:1-9. doi: 10.1016/j.jnutbio.2019.02.008. Epub 2019 Mar 12.
Folate-dependent one-carbon cycle metabolism (FOCM) plays a critical role in maintaining genomic stability through regulating DNA biosynthesis, repair and methylation. Folate metabolites as well as other metabolites in the FOCM are hypothesized to be altered when cells transition from normal to cancerous state. Using cells at different stages in their development into colorectal cancer, the FOCM metabolites were profiled as an effort to phenotype the cells, and the metabolite levels were compared to the expressions of related genes. Here, we investigate whether there is a correlation between the metabolite levels, DNA methylation levels and the expression of the related genes that drive the levels of these metabolites. Using CRL1459, APC10.1 HCT116 and Caco-2, we show for the first time that FOCM metabolites correlate with the gene expression patterns. These differences follow a trend that may facilitate distinguishing colon cells at the different stages as they transition into cancerous state. The folate distribution and methionine levels were found to be key in determining the staging of the colon cells in CRC development. Also, expression of CBS, MTRR and MAT genes may facilitate distinguishing between untransformed and transformed colon cells.
叶酸依赖性一碳循环代谢（FOCM）在通过调节 DNA 生物合成、修复和甲基化来维持基因组稳定性方面发挥着关键作用。当细胞从正常状态转变为癌状态时，叶酸代谢物以及 FOCM 中的其他代谢物被假设会发生改变。使用处于不同发育阶段的细胞发展为结直肠癌，对 FOCM 代谢物进行了分析，以努力表型化细胞，并将代谢物水平与相关基因的表达进行了比较。在这里，我们研究了代谢物水平、DNA 甲基化水平与驱动这些代谢物水平的相关基因表达之间是否存在相关性。使用 CRL1459、APC10.1 HCT116 和 Caco-2，我们首次表明 FOCM 代谢物与基因表达模式相关。这些差异遵循一种趋势，可能有助于区分在癌变过程中处于不同阶段的结肠细胞。叶酸分布和蛋氨酸水平被发现是决定 CRC 发展中结肠细胞分期的关键。此外，CBS、MTRR 和 MAT 基因的表达可能有助于区分未转化和转化的结肠细胞。
