Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.
Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran; Autoimmune Research Center, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.
Biomed Pharmacother. 2018 May;101:94-99. doi: 10.1016/j.biopha.2018.02.077. Epub 2018 Feb 23.
Growing evidence suggests a role of polyunsaturated fatty acids (PUFA) in the prevention of various types of malignancy, including colorectal cancer (CRC). No published studies have yet examined the direct effect of PUFA treatment on DNA methylation in CRC cells. In this study, 5 human CRC cells were treated with 100 μM DHA, EPA, and LA for 6 days and changes in their global- and gene-specific DNA methylation status as well as expression of DNA methyl transferases (DNMT) were investigated. Cell-type specific differences in DNA methylation and expression of DNMTs were observed in PUFA-treated cells. DHA and EPA treatment induced global hypermethylation in HT29/219 and HCT116 cells, but reduced methylation in Caco2 cells (p < 0.05). Among 10 tumor related genes tested in 5 CRC cell lines, DHA and EPA induced promoter demethylation of Cox2 in HT29/219, p14 and PPARγ in HCT116, and ECAD in SW742 cells. Cell-type specific differences in expression of DNMT1, DNMT3a, and 3b genes were also observed between PUFA-treated and control cells (p < 0.05). Overall, treatment of PUFAs coordinately induced the expression of DNMTs in HT29/219, but suppressed in other 4 cell lines investigated in this study.
越来越多的证据表明多不饱和脂肪酸（PUFA）在预防各种类型的恶性肿瘤，包括结直肠癌（CRC）方面发挥作用。目前还没有研究探讨 PUFA 处理对 CRC 细胞中 DNA 甲基化的直接影响。在这项研究中，用 100μM 的 DHA、EPA 和 LA 处理 5 个人类 CRC 细胞 6 天，研究它们的全基因组和基因特异性 DNA 甲基化状态以及 DNA 甲基转移酶（DNMT）的表达变化。在 PUFA 处理的细胞中观察到 DNA 甲基化和 DNMT 表达的细胞类型特异性差异。DHA 和 EPA 处理诱导 HT29/219 和 HCT116 细胞中的全基因组超甲基化，但降低 Caco2 细胞中的甲基化（p<0.05）。在 5 种 CRC 细胞系中测试的 10 个肿瘤相关基因中，DHA 和 EPA 诱导 HT29/219 中 Cox2、HCT116 中 p14 和 PPARγ 以及 SW742 细胞中 ECAD 的启动子去甲基化。在 PUFA 处理和对照细胞之间，也观察到 DNMT1、DNMT3a 和 3b 基因表达的细胞类型特异性差异（p<0.05）。总的来说，PUFA 处理协同诱导 HT29/219 中 DNMTs 的表达，但在本研究中研究的其他 4 种细胞系中抑制其表达。
