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泛素特异性蛋白酶7是胃癌的一个潜在治疗靶点。

Ubiquitin specific protease 7 is a potential therapeutic target for gastric cancer.

作者信息

Wang Zhi-Ru, Kang Wen-Ting, Yu Rui-Li

机构信息

Department of Pathology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China.

Clinical Operations Department, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Nanjing, Jiangsu, China.

出版信息

Front Oncol. 2025 Feb 21;15:1530924. doi: 10.3389/fonc.2025.1530924. eCollection 2025.

DOI:10.3389/fonc.2025.1530924
PMID:40061891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11885118/
Abstract

INTRODUCTION

As a deubiquitinase, ubiquitin-specific protease 7 (USP7) plays a vital role in diverse cancers, nevertheless, its role in gastric cancer (GC), which is the fifth leading cause of death in diverse cancers worldwide, has rarely been reported.

METHODS

To gain a comprehensive understanding about USP7 in the progression of GC, 287 paired GC tissues were collected and analyzed. ShRNA and small molecular inhibitor were used to investigate the impact of USP7 on cell proliferation. Additionally, xenograft proliferation was used to explore the effect of USP7 on tumor growth in animals.

RESULTS

We found that USP7 overexpression in GC tissues was correlated with several parameters of clinicopathology and poor disease-free survival rate. Meanwhile, the abrogation of USP7 suppressed GC cell proliferation by stabilizing p53 and promoting cell cycle arrest both in vitro and in vivo.

DISCUSSION

These results indicate that USP7 may serve as a biomarker for predicting the outcomes of patients with GC. Therefore, USP7 could be a promising therapeutic target for GC treatment.

摘要

引言

作为一种去泛素化酶,泛素特异性蛋白酶7(USP7)在多种癌症中发挥着至关重要的作用,然而,其在胃癌(GC)中的作用鲜有报道,而胃癌是全球各种癌症中导致死亡的第五大主要原因。

方法

为全面了解USP7在胃癌进展中的作用,收集并分析了287对胃癌组织。使用短发夹RNA(shRNA)和小分子抑制剂来研究USP7对细胞增殖的影响。此外,利用异种移植瘤增殖来探究USP7对动物肿瘤生长的作用。

结果

我们发现胃癌组织中USP7的过表达与临床病理学的几个参数以及无病生存率低相关。同时,USP7的缺失通过稳定p53和促进细胞周期停滞在体外和体内均抑制了胃癌细胞的增殖。

讨论

这些结果表明USP7可能作为预测胃癌患者预后的生物标志物。因此,USP7可能是胃癌治疗中一个有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/5ee83aab12ba/fonc-15-1530924-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/affe2879ff3e/fonc-15-1530924-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/67eba5253cd0/fonc-15-1530924-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/568a06866148/fonc-15-1530924-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/5ee83aab12ba/fonc-15-1530924-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/affe2879ff3e/fonc-15-1530924-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/67eba5253cd0/fonc-15-1530924-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/568a06866148/fonc-15-1530924-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0aa/11885118/5ee83aab12ba/fonc-15-1530924-g004.jpg

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USP7 Inhibitors Destabilize EBNA1 and Suppress Epstein-Barr Virus Tumorigenesis.USP7抑制剂使EBNA1不稳定并抑制爱泼斯坦-巴尔病毒的肿瘤发生。
J Med Virol. 2025 Jan;97(1):e70168. doi: 10.1002/jmv.70168.
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USP7 deubiquitinates KRAS and promotes non-small cell lung cancer.USP7 去泛素化 KRAS 并促进非小细胞肺癌。
Cell Rep. 2024 Nov 26;43(11):114917. doi: 10.1016/j.celrep.2024.114917. Epub 2024 Nov 4.
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VGLL3 modulates chemosensitivity through promoting DNA double-strand break repair.VGLL3 通过促进 DNA 双链断裂修复来调节化学敏感性。
Sci Adv. 2024 Oct 11;10(41):eadr2643. doi: 10.1126/sciadv.adr2643. Epub 2024 Oct 9.
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Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.泛素化和去泛素化在癌症中的作用:从机制到新的治疗方法。
Mol Cancer. 2024 Jul 25;23(1):148. doi: 10.1186/s12943-024-02046-3.
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p53/MDM2 signaling pathway in aging, senescence and tumorigenesis.p53/MDM2 信号通路在衰老、衰老和肿瘤发生中的作用。
Semin Cancer Biol. 2024 Jun;101:44-57. doi: 10.1016/j.semcancer.2024.05.001. Epub 2024 May 17.
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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据:全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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