Indole-3-carbinol (I3C) is a naturally occurring glucosinolate found in Brassica vegetables that is usually converted in gastric acidic environment to the efficient metabolite 3,3′-diindolylmethane (DIM). Both indoles (I3C and DIM) are known chemopreventive agents for various cancers including breast cancer. This study aimed to investigate the influence of both indoles on the tumor suppressor miRNAs (let-7a-e, miR-15a, miR-16, miR-17-5p, miR-19a, and miR-20a) and oncomiRs (miR-181a, miR-181b, miR-210, miR-221, and miR-106a), which are controlling the cell cycle key regulators: cyclin-dependent kinases (CDKs), CDK inhibitor p27^Kip1, and cyclin D1. Our results indicated that both indoles generally elevated the expression of the tumor suppressor miRNAs let-7a-e, miR-19a, miR-17-5p, and miR-20a and decreased the expression of the oncomiR list. Both indoles were able to significantly suppress the expression of CDK4 and CDK6 as well as the apoptotic markers Bcl-2 and survivin. Both indoles decreased cyclin-D1 protein, where I3C decreased cytoplasmic and nuclear cyclin-D1 significantly. Cytoplasmic and nuclear P27^Kip1 showed overexpression following treatment with I3C higher than that detected following DIM treatment. This study provides a mechanistic elucidation of the previously reported cell cycle arrest by I3C and DIM in breast cancer cells suggesting that this effect could be through modulation of miRNAs expression that, in turn, regulates the genetic network controlling the G1/S phase in cell cycle progression.

Indole-3-carbinol (I3C) 是一种天然存在于芸苔属蔬菜中的硫代葡萄糖苷，通常在胃酸环境中转化为有效的代谢物 3,3'-二吲哚甲烷 (DIM)。两种吲哚（I3C 和 DIM）都是已知的多种癌症（包括乳腺癌）的化学预防剂。本研究旨在研究吲哚对肿瘤抑制基因 miRNA（let-7a-e、miR-15a、miR-16、miR-17-5p、miR-19a 和 miR-20a）和肿瘤抑制基因 miRNA（miR- 181a、miR-181b、miR-210、miR-221 和 miR-106a），它们控制细胞周期的关键调节因子：细胞周期蛋白依赖性激酶 (CDK)、CDK 抑制剂 p27 ^Kip1和细胞周期蛋白 D1。我们的结果表明，两种吲哚通常都会提高肿瘤抑制基因 miRNA let-7a-e、miR-19a、miR-17-5p 和 miR-20a 的表达，并降低 oncomiR 列表的表达。两种吲哚都能显着抑制 CDK4 和 CDK6 以及凋亡标志物 Bcl-2 和存活蛋白的表达。两种吲哚均降低细胞周期蛋白-D1 蛋白，其中 I3C 显着降低细胞质和核细胞周期蛋白-D1。细胞质和核 P27 ^Kip1在用 I3C 处理后显示过表达高于在 DIM 处理后检测到的。这项研究提供了先前报道的乳腺癌细胞中 I3C 和 DIM 细胞周期停滞的机制阐明，表明这种作用可能是通过调节 miRNA 表达，进而调节控制细胞周期 G1/S 期的遗传网络进展。