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姜烯酚通过下调 miR-124-3p 抑制乳腺癌干细胞自我更新和肿瘤发生

The Role of MicroRNA-124-3p in Breast Cancer Stem Cell Inhibition by Benzyl Isothiocyanate.

机构信息

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.

出版信息

Pharm Res. 2024 Oct;41(10):1921-1932. doi: 10.1007/s11095-024-03775-2. Epub 2024 Oct 7.

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

These findings indicate that miR-124-3p plays an important role in BITC-mediated inhibition of bCSC.

摘要

目的

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。

方法

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。

结果

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。

结论

这些发现表明 miR-124-3p 在 BITC 介导的 bCSC 抑制中发挥重要作用。

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