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

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY Pharmaceutical Research Pub Date : 2024-10-01 Epub Date: 2024-10-07 DOI:10.1007/s11095-024-03775-2

Su-Hyeong Kim, Shivendra V Singh

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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 ^high/CD133^high 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.

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微RNA-124-3p在异硫氰酸苄酯抑制乳腺癌干细胞中的作用

目的：我们以前研究发现，从十字花科蔬菜中提取的异硫氰酸苄酯（BITC）可抑制乳腺癌干样细胞（bCSC）的自我更新。本研究深入探讨了BITC抑制乳腺癌干细胞的机制：方法：采用定量实时聚合酶链反应和Western印迹分析分别检测微RNA（miRNA）和叉头盒Q1（FoxQ1）蛋白的表达。通过醛脱氢酶1活性和流式细胞分析CD49f高/CD133高部分对bCSC进行定性：miR-124-3p并不影响BITC介导的细胞迁移或细胞增殖抑制作用，但它能显著调控BITC作用下的bCSC。我们还发现，miR-124-3p 直接靶向 FoxQ1 的 3'非翻译区（UTR），并负向调控其表达。miR-124-3p抑制剂部分减弱了BITC介导的对bCSC的抑制作用：这些研究结果表明，miR-124-3p 在 BITC 介导的 bCSC 抑制过程中发挥了重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.