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铜纳米颗粒对乳腺癌亚型中角蛋白19(KRT19)基因表达的影响:整合实验和生物信息学方法

Impact of Copper Nanoparticles on Keratin 19 (KRT19) Gene Expression in Breast Cancer Subtypes: Integrating Experimental and Bioinformatics Approaches.

作者信息

Taha Safa, Sultan Ameera, Aljishi Muna, Greish Khaled

机构信息

Princess Al-Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama 26671, Bahrain.

出版信息

Int J Mol Sci. 2025 Jul 27;26(15):7269. doi: 10.3390/ijms26157269.

DOI:10.3390/ijms26157269
PMID:40806403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12346958/
Abstract

This study investigates the effects of copper nanoparticles (CuNPs) on KRT19 gene expression in four breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF7, and T47D), representing triple-negative and luminal subtypes. Using cytotoxicity assays, quantitative RT-PCR, and bioinformatics tools (STRING, g:Profiler), we demonstrate subtype-specific, dose-dependent KRT19 suppression, with epithelial-like cell lines showing greater sensitivity. CuNPs, characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) with a mean size of 179 ± 15 nm, exhibited dose-dependent cytotoxicity. Bioinformatics analyses suggest KRT19's potential as a biomarker for CuNP-based therapies, pending in vivo and clinical validation. These findings highlight CuNPs' therapeutic potential and the need for further studies to optimize their application in personalized breast cancer treatment.

摘要

本研究调查了铜纳米颗粒(CuNPs)对四种乳腺癌细胞系(MDA-MB-231、MDA-MB-468、MCF7和T47D)中KRT19基因表达的影响,这些细胞系代表三阴性和管腔亚型。通过细胞毒性测定、定量逆转录聚合酶链反应(RT-PCR)和生物信息学工具(STRING、g:Profiler),我们证明了KRT19的抑制具有亚型特异性和剂量依赖性,上皮样细胞系表现出更高的敏感性。通过动态光散射(DLS)和透射电子显微镜(TEM)表征的平均尺寸为179±15nm的CuNPs表现出剂量依赖性细胞毒性。生物信息学分析表明,KRT19有潜力作为基于CuNP疗法的生物标志物,但有待体内和临床验证。这些发现突出了CuNPs的治疗潜力以及进一步研究以优化其在个性化乳腺癌治疗中应用的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/1368ca82b082/ijms-26-07269-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/bbba02d54697/ijms-26-07269-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/577f4d8fd16c/ijms-26-07269-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/1368ca82b082/ijms-26-07269-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/bbba02d54697/ijms-26-07269-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/b35751748857/ijms-26-07269-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/5a0680cddc15/ijms-26-07269-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/577f4d8fd16c/ijms-26-07269-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c04/12346958/1368ca82b082/ijms-26-07269-g005.jpg

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本文引用的文献

1
Keratin 19 (Krt19) is a novel marker gene for epicardial cells.角蛋白19(Krt19)是心外膜细胞的一种新型标志物基因。
Front Genet. 2024 May 20;15:1385867. doi: 10.3389/fgene.2024.1385867. eCollection 2024.
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Cancer statistics, 2023.癌症统计数据,2023 年。
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Keratin 19 regulates cell cycle pathway and sensitivity of breast cancer cells to CDK inhibitors.角蛋白 19 调节细胞周期途径和乳腺癌细胞对 CDK 抑制剂的敏感性。
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g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update).g:Profiler:一个用于功能富集分析和基因列表转换的网络服务器(2019 更新)。
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STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets.STRING v11:具有增强覆盖范围的蛋白质-蛋白质相互作用网络,支持在全基因组实验数据集的功能发现。
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