• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

依鲁替尼通过靶向 HuR 蛋白抑制乳腺癌转移。

Eltrombopag Inhibits Metastasis in Breast Carcinoma by Targeting HuR Protein.

机构信息

The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Shanghai Frontiers Science Center for Traditional Chinese Medicine Chemical Biology, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Int J Mol Sci. 2023 Feb 5;24(4):3164. doi: 10.3390/ijms24043164.

DOI:10.3390/ijms24043164
PMID:36834574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9963984/
Abstract

Eltrombopag is a small molecule TPO-R agonist that has been shown in our previous studies to inhibit tumor growth by targeting Human antigen R (HuR) protein. HuR protein not only regulates the mRNA stability of tumor growth-related genes, but it also regulates the mRNA stability of a variety of cancer metastasis-related genes, such as , , and . However, the role and mechanisms of eltrombopag in breast cancer metastasis have not been fully investigated. The purpose of this study was to investigate whether eltrombopag can inhibit breast cancer metastasis by targeting HuR. Our study first found that eltrombopag can destroy HuR-AU-rich element (ARE) complexes at the molecular level. Secondly, eltrombopag was found to suppress 4T1 cell migration and invasion and inhibit macrophage-mediated lymphangiogenesis at the cellular level. In addition, eltrombopag exerted inhibitory effects on lung and lymph node metastasis in animal tumor metastasis models. Finally, it was verified that eltrombopag inhibited the expressions of , , and in 4T1 cells and in RAW264.7 cells by targeting HuR. In conclusion, eltrombopag displayed antimetastatic activity in breast cancer in an HuR dependent manner, which may provide a novel application for eltrombopag, hinting at the multiple effects of HuR inhibitors in cancer therapy.

摘要

依洛尤单抗是一种小分子 TPO-R 激动剂，我们之前的研究表明，它通过靶向人抗原 R（HuR）蛋白来抑制肿瘤生长。HuR 蛋白不仅调节肿瘤生长相关基因的 mRNA 稳定性，还调节多种癌症转移相关基因的 mRNA 稳定性，如 、 、 。然而，依洛尤单抗在乳腺癌转移中的作用和机制尚未被充分研究。本研究旨在探讨依洛尤单抗是否可以通过靶向 HuR 来抑制乳腺癌转移。我们的研究首先发现，依洛尤单抗可以在分子水平上破坏 HuR-AU 丰富元件（ARE）复合物。其次，在细胞水平上发现依洛尤单抗可以抑制 4T1 细胞迁移和侵袭，并抑制巨噬细胞介导的淋巴管生成。此外，依洛尤单抗在动物肿瘤转移模型中对肺和淋巴结转移发挥抑制作用。最后，通过靶向 HuR 验证了依洛尤单抗抑制 4T1 细胞和 RAW264.7 细胞中 和 的表达。综上所述，依洛尤单抗以 HuR 依赖的方式在乳腺癌中表现出抗转移活性，这可能为依洛尤单抗提供了一种新的应用，提示 HuR 抑制剂在癌症治疗中的多种作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/13b046837fe3/ijms-24-03164-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/337e1f2c3719/ijms-24-03164-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/3d157da4d37f/ijms-24-03164-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/4da64044be8a/ijms-24-03164-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/6964888463b0/ijms-24-03164-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/722b748c93ca/ijms-24-03164-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/71bccc49f9ff/ijms-24-03164-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/a4e940f4f697/ijms-24-03164-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/d70cb58f5999/ijms-24-03164-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/13b046837fe3/ijms-24-03164-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/337e1f2c3719/ijms-24-03164-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/3d157da4d37f/ijms-24-03164-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/4da64044be8a/ijms-24-03164-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/6964888463b0/ijms-24-03164-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/722b748c93ca/ijms-24-03164-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/71bccc49f9ff/ijms-24-03164-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/a4e940f4f697/ijms-24-03164-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/d70cb58f5999/ijms-24-03164-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b0/9963984/13b046837fe3/ijms-24-03164-g009.jpg

相似文献

1
Eltrombopag Inhibits Metastasis in Breast Carcinoma by Targeting HuR Protein.依鲁替尼通过靶向 HuR 蛋白抑制乳腺癌转移。
Int J Mol Sci. 2023 Feb 5;24(4):3164. doi: 10.3390/ijms24043164.
2
Discovery of the anti-angiogenesis effect of eltrombopag in breast cancer through targeting of HuR protein.通过靶向HuR蛋白发现艾曲泊帕在乳腺癌中的抗血管生成作用。
Acta Pharm Sin B. 2020 Aug;10(8):1414-1425. doi: 10.1016/j.apsb.2020.02.007. Epub 2020 Feb 24.
3
Human antigen R is positively associated with malignant aggressiveness via upregulation of cell proliferation, migration, and vascular endothelial growth factors and cyclooxygenase-2 in prostate cancer.人类抗原R通过上调前列腺癌细胞增殖、迁移、血管内皮生长因子和环氧合酶-2与恶性侵袭性呈正相关。
Transl Res. 2016 Sep;175:116-28. doi: 10.1016/j.trsl.2016.04.002. Epub 2016 Apr 29.
4
Muscone derivative ZM-32 inhibits breast tumor angiogenesis by suppressing HuR-mediated VEGF and MMP9 expression.麝香衍生物 ZM-32 通过抑制 HuR 介导的 VEGF 和 MMP9 表达抑制乳腺癌血管生成。
Biomed Pharmacother. 2021 Apr;136:111265. doi: 10.1016/j.biopha.2021.111265. Epub 2021 Jan 12.
5
HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium.HuR 通过稳定肿瘤内皮细胞中 VEGF 和 COX-2 的 mRNA 来保持血管生成开关。
Br J Cancer. 2011 Mar 1;104(5):819-29. doi: 10.1038/bjc.2011.20. Epub 2011 Feb 1.
6
Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients.在浸润性乳腺癌患者中，Hu抗原受体（HuR）表达升高与肿瘤侵袭性及预后不良相关，但与环氧合酶-2（COX-2）表达无关。
Pathol Oncol Res. 2018 Jul;24(3):631-640. doi: 10.1007/s12253-017-0288-1. Epub 2017 Aug 14.
7
Lentivirus-mediated small interfering RNA targeting VEGF-C inhibited tumor lymphangiogenesis and growth in breast carcinoma.慢病毒介导的靶向血管内皮生长因子C的小干扰RNA抑制乳腺癌肿瘤淋巴管生成和生长。
Anat Rec (Hoboken). 2009 May;292(5):633-9. doi: 10.1002/ar.20893.
8
Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis.靶向 RNA 结合蛋白 HuR 与 FOXQ1 的相互作用可抑制乳腺癌的侵袭和转移。
Commun Biol. 2020 Apr 24;3(1):193. doi: 10.1038/s42003-020-0933-1.
9
Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2.ELAV样蛋白HuR在人结肠癌中的表达：与肿瘤分期及环氧化酶-2的关系
Mod Pathol. 2006 Sep;19(9):1261-9. doi: 10.1038/modpathol.3800645. Epub 2006 Jun 23.
10
Impact of HuR inhibition by the small molecule MS-444 on colorectal cancer cell tumorigenesis.小分子MS-444抑制HuR对结肠癌细胞肿瘤发生的影响。
Oncotarget. 2016 Nov 8;7(45):74043-74058. doi: 10.18632/oncotarget.12189.

引用本文的文献

1
Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the β-Catenin Signaling Pathway.重楼皂苷I通过调控β-连环蛋白信号通路抑制宫颈癌转移。
Int J Mol Sci. 2025 May 12;26(10):4630. doi: 10.3390/ijms26104630.
2
Effects of genetic ablation and pharmacological inhibition of HuR on gene expression, iron metabolism, and hormone levels.HuR基因敲除和药物抑制对基因表达、铁代谢及激素水平的影响。
BMC Biol. 2025 Jan 23;23(1):24. doi: 10.1186/s12915-025-02131-z.

本文引用的文献

1
Cancer statistics for the year 2020: An overview.2020年癌症统计数据概述。
Int J Cancer. 2021 Apr 5. doi: 10.1002/ijc.33588.
2
Long Noncoding RNA VESTAR Regulates Lymphangiogenesis and Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma by Enhancing VEGFC mRNA Stability.长链非编码 RNA VESTAR 通过增强 VEGFC mRNA 稳定性调节食管鳞癌的淋巴管生成和淋巴结转移。
Cancer Res. 2021 Jun 15;81(12):3187-3199. doi: 10.1158/0008-5472.CAN-20-1713. Epub 2021 Mar 26.
3
Discovery of the anti-angiogenesis effect of eltrombopag in breast cancer through targeting of HuR protein.
通过靶向HuR蛋白发现艾曲泊帕在乳腺癌中的抗血管生成作用。
Acta Pharm Sin B. 2020 Aug;10(8):1414-1425. doi: 10.1016/j.apsb.2020.02.007. Epub 2020 Feb 24.
4
An RNA-Binding Protein, Hu-antigen R, in Pancreatic Cancer Epithelial to Mesenchymal Transition, Metastasis, and Cancer Stem Cells.RNA 结合蛋白 Hu 抗原 R 在胰腺癌上皮间质转化、转移和癌症干细胞中的作用。
Mol Cancer Ther. 2020 Nov;19(11):2267-2277. doi: 10.1158/1535-7163.MCT-19-0822. Epub 2020 Sep 2.
5
Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis.靶向 RNA 结合蛋白 HuR 与 FOXQ1 的相互作用可抑制乳腺癌的侵袭和转移。
Commun Biol. 2020 Apr 24;3(1):193. doi: 10.1038/s42003-020-0933-1.
6
Mechanism of angiogenesis promotion with Shexiang Baoxin Pills by regulating function and signaling pathway of endothelial cells through macrophages.麝香保心丸通过调节巨噬细胞功能及信号通路促进血管生成的机制。
Atherosclerosis. 2020 Jan;292:99-111. doi: 10.1016/j.atherosclerosis.2019.11.005. Epub 2019 Nov 15.
7
UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis.UDP-葡萄糖加速 SNAI1 mRNA 衰减并损害肺癌转移。
Nature. 2019 Jul;571(7763):127-131. doi: 10.1038/s41586-019-1340-y. Epub 2019 Jun 26.
8
Thrombopoietin receptor agonists: ten years later.血小板生成素受体激动剂：十年后。
Haematologica. 2019 Jun;104(6):1112-1123. doi: 10.3324/haematol.2018.212845. Epub 2019 May 9.
9
Innate effector cells in angiogenesis and lymphangiogenesis.先天效应细胞在血管生成和淋巴管生成中的作用。
Curr Opin Immunol. 2018 Aug;53:152-160. doi: 10.1016/j.coi.2018.05.002. Epub 2018 May 17.
10
Interfering with HuR-RNA Interaction: Design, Synthesis and Biological Characterization of Tanshinone Mimics as Novel, Effective HuR Inhibitors.干扰 HuR-RNA 相互作用：丹参酮类似物作为新型有效 HuR 抑制剂的设计、合成与生物学特征研究。
J Med Chem. 2018 Feb 22;61(4):1483-1498. doi: 10.1021/acs.jmedchem.7b01176. Epub 2018 Jan 31.