UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, 2.32A Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Pharm Res. 2024 Oct;41(10):1921-1932. doi: 10.1007/s11095-024-03775-2. Epub 2024 Oct 7.
We have shown previously that benzyl isothiocyanate (BITC) derived from cruciferous vegetables inhibits self-renewal of breast cancer stem-like cells (bCSC). The current study provides insights into the mechanism of bCSC inhibition by BITC.
Quantitative real time-polymerase chain reaction and western blot analysis were performed to detect microRNAs (miRNAs) and Forkhead box Q1 (FoxQ1) protein expression, respectively. The bCSC were characterized by aldehyde dehydrogenase 1 activity and flow cytometric analysis of CD49f /CD133 fraction.
BITC treatment resulted in induction of miR-124-3p expression in MDA-MB-231 and MCF-7 cells. miR-124-3p did not affect BITC-mediated inhibition of cell migration or cell proliferation but it significantly regulated bCSC in response to BITC. We also found that miR-124-3p directly targets the 3'untranslated regions (UTR) of FoxQ1 and negatively regulates its expression. The BITC-mediated inhibition of bCSC was partially attenuated by miR-124-3p inhibitor.
These findings indicate that miR-124-3p plays an important role in BITC-mediated inhibition of bCSC.
我们之前已经证明,来自十字花科蔬菜的苄基异硫氰酸酯(BITC)抑制乳腺癌干细胞样细胞(bCSC)的自我更新。本研究深入了解了 BITC 抑制 bCSC 的机制。
通过定量实时聚合酶链反应和 Western blot 分析分别检测 microRNAs(miRNAs)和叉头框 Q1(FoxQ1)蛋白表达。通过醛脱氢酶 1 活性和 CD49f/CD133 亚群的流式细胞术分析来鉴定 bCSC。
BITC 处理导致 MDA-MB-231 和 MCF-7 细胞中 miR-124-3p 的表达诱导。miR-124-3p 不影响 BITC 介导的细胞迁移或细胞增殖的抑制,但它显著调节 bCSC 对 BITC 的反应。我们还发现,miR-124-3p 直接靶向 FoxQ1 的 3'非翻译区(UTR)并负调控其表达。miR-124-3p 抑制剂部分减弱了 BITC 介导的 bCSC 抑制。
这些发现表明 miR-124-3p 在 BITC 介导的 bCSC 抑制中发挥重要作用。