School of Public Health, Chengdu Medical College, Chengdu, China.
Cancer Sci. 2019 Oct;110(10):3089-3097. doi: 10.1111/cas.14133. Epub 2019 Sep 16.
Delphinidin, one of the main anthocyanidins, has potent anti-cancer properties. In this study, we investigated the effect of delphinidin on 1-methyl-1-nitrosourea (MNU)-induced breast carcinogenesis on rats and the mechanism of delphinidin via negative regulation of the HOTAIR/microRNA-34a axis. We found administration of delphinidin could effectively suppress MNU-induced mammal breast carcinogenesis. Delphinidin downregulated the level of HOTAIR and upregulated miR-34a in breast carcinogenesis. Western blot analysis confirmed that delphinidin treatment can significantly decrease the expression of β-catenin, glycogen synthase kinase-3β (Gsk3β), c-Myc, cyclin-D1, and matrix metalloproteinase-7(MMP-7) expression in breast cancer cells, and inhibition of miR-34a significantly reduced the effect of delphinidin on c-Myc, cyclin-D1, and MMP-7. HOTAIR overexpression also blocked the effect of delphinidin on miR-34a and the Wnt/β-catenin signaling pathway in MDA-MB-231 cells. RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay results showed that delphinidin upregulated miR-34a by inhibiting HOTAIR, coupled with enhancement of the zeste homolog 2 (EZH2) and histone H3 Lys27 trimethylation (H3K27me3). This study indicated that delphinidin may potentially suppress breast carcinogenesis and exert its anti-cancer effect through the HOTAIR/miR-34a axis. These findings provided new evidence for the use of delphinidin in preventing breast carcinogenesis.
飞燕草素是主要的花色苷之一，具有很强的抗癌特性。在这项研究中，我们研究了飞燕草素对 MNU 诱导的大鼠乳腺癌发生的影响，以及通过负调控 HOTAIR/miR-34a 轴来发挥其作用的机制。我们发现，给予飞燕草素可以有效抑制 MNU 诱导的哺乳动物乳腺肿瘤发生。飞燕草素下调乳腺癌发生过程中的 HOTAIR 水平，并上调 miR-34a。Western blot 分析证实，飞燕草素处理可显著降低乳腺癌细胞中β-catenin、糖原合成酶激酶-3β (Gsk3β)、c-Myc、细胞周期蛋白 D1 和基质金属蛋白酶-7(MMP-7)的表达，而 miR-34a 的抑制则显著降低了飞燕草素对 c-Myc、细胞周期蛋白 D1 和 MMP-7 的作用。HOTAIR 的过表达也阻断了飞燕草素对 MDA-MB-231 细胞中 miR-34a 和 Wnt/β-catenin 信号通路的作用。RNA 免疫沉淀（RIP）和染色质免疫沉淀（ChIP）实验结果表明，飞燕草素通过抑制 HOTAIR 而上调 miR-34a，同时增强了 EZH2 和组蛋白 H3 Lys27 三甲基化（H3K27me3）。这项研究表明，飞燕草素可能通过 HOTAIR/miR-34a 轴抑制乳腺肿瘤发生并发挥其抗癌作用。这些发现为使用飞燕草素预防乳腺肿瘤发生提供了新的证据。
