Omics A Journal of Integrative Biology, 2015, 19(4):209-19.

Genome-Wide DNA Methylation Modified by Soy Phytoestrogens: Role for Epigenetic Therapeutics in Prostate Cancer?

Seher Karsli-Ceppioglu, Marjolaine Ngollo, et al

Department of Oncogenetics, Centre Jean Perrin-CBRV , Dunant, Clermont-Ferrand, France; et al

In prostate cancer, DNA methylation is significantly associated with tumor initiation, progression, and metastasis. Previous studies have suggested that soy phytoestrogens might regulate DNA methylation at individual candidate gene loci and that they play a crucial role as potential therapeutic agents for prostate cancer. The purpose of our study was to examine the modulation effects of phytoestrogens on a genome-wide scale in regards to DNA methylation in prostate cancer. Prostate cancer cell lines DU-145 and LNCaP were treated with 40 μM of genistein and 110 μM of daidzein. DNMT inhibitor 5-azacytidine (2 μM) and the methylating agent budesonide (2 μM) were used to compare their demethylation/methylation effects with phytoestrogens. The regulatory effects of phytoestrogens on DNA methylation were analyzed by using a methyl-DNA immunoprecipitation method coupled with Human DNA Methylation Microarrays (MeDIP-chip). We observed that the methylation profiles of 58 genes were altered by genistein and daidzein treatments in DU-145 and LNCaP prostate cancer cells. In addition, the methylation frequencies of the MAD1L1, TRAF7, KDM4B, and hTERT genes were remarkably modified by genistein treatment. Our results suggest that the modulation effects of phytoestrogens on DNA methylation essentially lead to inhibition of cell growth and induction of apoptosis. Genome-wide methylation profiling reported here suggests that epigenetic regulation mechanisms and, by extension, epigenetics-driven novel therapeutic candidates warrant further consideration in future "omics" studies of prostate cancer.

美国《组学：综合生物学杂志》4月

大豆植物雌激素对全基因组的 DNA 甲基化改性︰ 表观遗传疗法在前列腺癌中的作用？

瑟黑 喀丝丽 塞皮格鲁，玛乔莱恩·南戈洛，等

法国吉恩佩林-CBRV中心肿瘤部等

在前列腺癌中，DNA甲基化与肿瘤起始，进展和转移显著相关。 以前的研究表明，大豆植物雌激素可能调节个体候选基因位点的DNA甲基化，并且作为前列腺癌的潜在治疗剂它们起了关键作用。 我们研究的目的是检查植物雌激素对前列腺癌DNA甲基化的基因组范围的调节作用。用40μM的金雀异黄素和110μM的黄豆苷元处理 前列腺癌细胞株DU-145和LNCaP。 使用DNMT抑制剂5-氮杂胞苷（2μM）和甲基化布地奈德（2μM）来比较它们对植物雌激素的去甲基化/甲基化作用。 通过使用与人体DNA甲基化微阵列（MeDIP-chip）连接的甲基DNA免疫沉淀方法分析植物雌激素对DNA甲基化的调节作用。我们观察到在DU-145和LNCaP前列腺癌细胞中58种基因的甲基化谱因为金雀异黄素和黄豆苷原处理所改变。 此外，通过金雀异黄素处理，MAD1L1，TRAF7，KDM4B和hTERT基因的甲基化频率明显改变。 我们的研究结果表明植物雌激素对DNA甲基化的调节作用基本上导致细胞生长的抑制和细胞凋亡的诱导。 这里报道的全基因组甲基化分析表明，表观遗传调控机制及其延伸，表观遗传学驱动的新型治疗候选方案在未来前列腺癌的“组学”研究值得进一步考虑。