• 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

FOXA1 依赖性 PUS1 通过一种非酶途径调节 EIF3b 稳定性，介导前列腺癌骨转移。

FOXA1-dependent PUS1 regulates EIF3b stability in a non-enzymatic pathway mediating prostate cancer bone metastasis.

机构信息

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.

Department of Urology, Nanfang hospital, Southern Medical University, Guangzhou 510515, China.

出版信息

Int J Biol Sci. 2024 Aug 19;20(11):4566-4584. doi: 10.7150/ijbs.100905. eCollection 2024.

DOI:10.7150/ijbs.100905
PMID:39247811
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11380452/
Abstract

Bone metastasis is a significant contributor to the poor prognosis in prostate cancer. Recent evidence highlights the pivotal role of pseudouridine synthases in solid tumor progression, yet the specific enzyme driving prostate cancer metastasis remains unidentified. This study uncovers a novel regulatory mechanism of the FOXA1/PUS1/EIF3b signaling axis in prostate cancer bone metastasis. We identified elevated PUS1 expression in prostate cancer tissues, correlating with higher clinical grade and worse prognosis. Knockdown of PUS1 inhibited metastasis independently of its enzymatic activity, with EIF3b acting as a downstream effector, protected from ubiquitin-mediated degradation by PUS1. Overexpression of EIF3b countered the metastasis suppression due to PUS1 knockdown. Additionally, FOXA1 was shown to enhance PUS1 expression by binding to its promoter. Mogroside IV-E, a specific PUS1 inhibitor, demonstrated potent anti-metastatic effects by reducing PUS1 expression. Our findings highlight the FOXA1/PUS1/EIF3b axis as a critical mediator of prostate cancer bone metastasis and suggest that targeting this pathway could be a promising therapeutic strategy.

摘要

骨转移是前列腺癌预后不良的重要因素。最近的证据强调了假尿嘧啶合酶在实体瘤进展中的关键作用，但驱动前列腺癌转移的确切酶仍未确定。本研究揭示了 FOXA1/PUS1/EIF3b 信号轴在前列腺癌骨转移中的新调控机制。我们发现前列腺癌组织中 PUS1 表达升高，与较高的临床分级和较差的预后相关。PUS1 的敲低抑制了转移，独立于其酶活性，EIF3b 作为下游效应物，通过 PUS1 免受泛素介导的降解而得到保护。EIF3b 的过表达抵消了由于 PUS1 敲低导致的转移抑制。此外，FOXA1 通过结合其启动子增强 PUS1 的表达。Mogroside IV-E 是一种特异性 PUS1 抑制剂，通过降低 PUS1 表达显示出强大的抗转移作用。我们的研究结果强调了 FOXA1/PUS1/EIF3b 轴作为前列腺癌骨转移的关键介质，并表明靶向该途径可能是一种有前途的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/0d493eb22429/ijbsv20p4566g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/92ba10e3491d/ijbsv20p4566g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/48695815a511/ijbsv20p4566g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/5b0d2dea1b57/ijbsv20p4566g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/74981098f0b1/ijbsv20p4566g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/795609345d76/ijbsv20p4566g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/347faf7c2012/ijbsv20p4566g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/5d4e743e66a2/ijbsv20p4566g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/0d493eb22429/ijbsv20p4566g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/92ba10e3491d/ijbsv20p4566g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/48695815a511/ijbsv20p4566g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/5b0d2dea1b57/ijbsv20p4566g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/74981098f0b1/ijbsv20p4566g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/795609345d76/ijbsv20p4566g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/347faf7c2012/ijbsv20p4566g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/5d4e743e66a2/ijbsv20p4566g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/808c/11380452/0d493eb22429/ijbsv20p4566g008.jpg

相似文献

1
FOXA1-dependent PUS1 regulates EIF3b stability in a non-enzymatic pathway mediating prostate cancer bone metastasis.FOXA1 依赖性 PUS1 通过一种非酶途径调节 EIF3b 稳定性，介导前列腺癌骨转移。
Int J Biol Sci. 2024 Aug 19;20(11):4566-4584. doi: 10.7150/ijbs.100905. eCollection 2024.
2
Eukaryotic translation initiation factor 3 subunit b is a novel oncogenic factor in prostate cancer.真核翻译起始因子 3 亚基 b 是前列腺癌中的一种新型致癌因子。
Mamm Genome. 2020 Aug;31(7-8):197-204. doi: 10.1007/s00335-020-09842-4. Epub 2020 Jun 15.
3
Androgen receptor-independent function of FoxA1 in prostate cancer metastasis.FoxA1 在前列腺癌转移中的雄激素受体非依赖性功能。
Cancer Res. 2013 Jun 15;73(12):3725-36. doi: 10.1158/0008-5472.CAN-12-3468. Epub 2013 Mar 28.
4
Translation initiation factor eIF3b expression in human cancer and its role in tumor growth and lung colonization.翻译起始因子 eIF3b 在人类癌症中的表达及其在肿瘤生长和肺转移中的作用。
Clin Cancer Res. 2013 Jun 1;19(11):2850-60. doi: 10.1158/1078-0432.CCR-12-3084. Epub 2013 Apr 10.
5
Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer.晚期前列腺癌中 FOXA1 激活突变的不同结构类别。
Nature. 2019 Jul;571(7765):413-418. doi: 10.1038/s41586-019-1347-4. Epub 2019 Jun 26.
6
FOXA1 promotes tumor progression in prostate cancer via the insulin-like growth factor binding protein 3 pathway.FOXA1 通过胰岛素样生长因子结合蛋白 3 途径促进前列腺癌的肿瘤进展。
PLoS One. 2012;7(8):e42456. doi: 10.1371/journal.pone.0042456. Epub 2012 Aug 3.
7
Genetic features of TP53 mutation and its downstream FOXA1 in prostate cancer.前列腺癌中 TP53 突变及其下游 FOXA1 的遗传特征。
Biosci Trends. 2022 Jul 20;16(3):221-229. doi: 10.5582/bst.2022.01235. Epub 2022 Jun 28.
8
m A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2-mediated IGF1R mRNA stabilization.lncRNA PCAT6 的修饰通过 IGF2BP2 介导的 IGF1R mRNA 稳定促进前列腺癌骨转移。
Clin Transl Med. 2021 Jun;11(6):e426. doi: 10.1002/ctm2.426.
9
FOXA1 modulates EAF2 regulation of AR transcriptional activity, cell proliferation, and migration in prostate cancer cells.叉头框蛋白A1（FOXA1）调节EAF2对前列腺癌细胞中雄激素受体（AR）转录活性、细胞增殖和迁移的调控。
Prostate. 2015 Jun 15;75(9):976-87. doi: 10.1002/pros.22982. Epub 2015 Mar 23.
10
FOXA1 promotes prostate cancer angiogenesis by inducing multiple pro-angiogenic factors expression.FOXA1 通过诱导多种促血管生成因子的表达促进前列腺癌血管生成。
J Cancer Res Clin Oncol. 2021 Nov;147(11):3225-3243. doi: 10.1007/s00432-021-03730-3. Epub 2021 Jul 14.

引用本文的文献

1
EIF3B stabilizes MAP2K2 to activate the ERK pathway and promote the progression of laryngeal squamous cell carcinoma.真核翻译起始因子3B（EIF3B）稳定丝裂原活化蛋白激酶激酶2（MAP2K2）以激活细胞外信号调节激酶（ERK）通路并促进喉鳞状细胞癌进展。
Cell Death Discov. 2025 Jul 21;11(1):333. doi: 10.1038/s41420-025-02634-2.
2
Prostate cancer cell-derived exosomes inhibit macrophage phagocytosis through EIF3B-mediated exosomal sorting of miR-100-5p.前列腺癌细胞衍生的外泌体通过EIF3B介导的miR-100-5p外泌体分选抑制巨噬细胞吞噬作用。
Sci Rep. 2025 Jul 18;15(1):26138. doi: 10.1038/s41598-025-11799-w.
3
Antiviral effects of mogroside V against porcine reproductive and respiratory syndrome virus .

本文引用的文献

1
EIF3B stabilizes PCNA by counteracting SYVN1-mediated ubiquitination to serve as a promotor in cholangiocarcinoma.EIF3B 通过拮抗 SYVN1 介导的泛素化稳定 PCNA，从而在胆管癌中作为一个促进子发挥作用。
Aging (Albany NY). 2024 Apr 29;16(8):7311-7330. doi: 10.18632/aging.205759.
2
KIF18A inactivates hepatic stellate cells and alleviates liver fibrosis through the TTC3/Akt/mTOR pathway.KIF18A 通过 TTC3/Akt/mTOR 通路抑制肝星状细胞活化进而缓解肝纤维化。
Cell Mol Life Sci. 2024 Feb 19;81(1):96. doi: 10.1007/s00018-024-05114-5.
3
Cancer statistics, 2024.
罗汉果甜苷V对猪繁殖与呼吸综合征病毒的抗病毒作用
Front Microbiol. 2025 Jul 2;16:1611600. doi: 10.3389/fmicb.2025.1611600. eCollection 2025.
4
Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) Before Treatment as the Predictive Indicators for Bone Metastasis in Prostate Cancer Patients.老年营养风险指数（GNRI）和治疗前预后营养指数（PNI）作为前列腺癌患者骨转移的预测指标
Int J Gen Med. 2025 May 24;18:2703-2713. doi: 10.2147/IJGM.S516768. eCollection 2025.
2024年癌症统计数据。
CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.
4
A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3.一种编码蛋白质的CCDC7环状RNA通过上调FLRT3抑制前列腺癌进展。
NPJ Precis Oncol. 2024 Jan 16;8(1):11. doi: 10.1038/s41698-024-00503-2.
5
Local Treatment and Treatment-Related Adverse Effects Among Patients With Advanced Prostate Cancer.局部治疗与晚期前列腺癌患者的治疗相关不良反应。
JAMA Netw Open. 2023 Dec 1;6(12):e2348057. doi: 10.1001/jamanetworkopen.2023.48057.
6
MT1G, an emerging ferroptosis-related gene: A novel prognostic biomarker and indicator of immunotherapy sensitivity in prostate cancer.MT1G，一个新兴的铁死亡相关基因：前列腺癌中一个新的预后生物标志物和免疫治疗敏感性的指标。
Environ Toxicol. 2024 Feb;39(2):927-941. doi: 10.1002/tox.23997. Epub 2023 Nov 16.
7
The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment.关键的细胞衰老相关分子RRM2调节前列腺癌的进展以及对多西他赛治疗的抗性。
Cell Biosci. 2023 Nov 15;13(1):211. doi: 10.1186/s13578-023-01157-6.
8
Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance and Immune Evasion in Lethal Prostate Cancer.主转录因子重编程释放选择性翻译促进致命性前列腺癌的去势抵抗和免疫逃逸。
Cancer Discov. 2023 Dec 12;13(12):2584-2609. doi: 10.1158/2159-8290.CD-23-0306.
9
HIF1A-repressed PUS10 regulates NUDC/Cofilin1 dependent renal cell carcinoma migration by promoting the maturation of miR-194-5p.HIF1A抑制的PUS10通过促进miR-194-5p的成熟来调节NUDC/丝切蛋白1依赖性肾细胞癌的迁移。
Cell Biosci. 2023 Aug 18;13(1):153. doi: 10.1186/s13578-023-01094-4.
10
TSPAN18 facilitates bone metastasis of prostate cancer by protecting STIM1 from TRIM32-mediated ubiquitination.TSPAN18 通过保护 STIM1 免受 TRIM32 介导的泛素化来促进前列腺癌的骨转移。
J Exp Clin Cancer Res. 2023 Aug 5;42(1):195. doi: 10.1186/s13046-023-02764-4.