USP31 Activates the Wnt/β-catenin Signaling Pathway and Promotes Gastric Cancer Cell Proliferation, Invasion and Migration.

Lan Li, Limin Ye, Yinying Cui, Yueting Wu, Ling Shui, Zheng Zong, Zhao Nie
{"title":"USP31 Activates the Wnt/β-catenin Signaling Pathway and Promotes Gastric Cancer Cell Proliferation, Invasion and Migration.","authors":"Lan Li, Limin Ye, Yinying Cui, Yueting Wu, Ling Shui, Zheng Zong, Zhao Nie","doi":"10.2174/0115748928297343240425055552","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) has a poor prognosis because it is highly aggressive, yet there are currently few effective therapies available. Although protein ubiquitination has been shown to play a complex role in the development of gastric cancer, to date, no efficient ubiquitinating enzymes have been identified as treatment targets for GC.</p><p><strong>Methods: </strong>The TCGA database was used for bioinformatic investigation of ubiquitin-specific protease 31 (USP31) expression in GC, and experimental techniques, including Western blotting, qRT-PCR, and immunohistochemistry, were used to confirm the findings. We also analyzed the relationship between USP31 expression and clinical prognosis in patients with GC. We further investigated the effects of USP31 on the proliferation, invasion, migration, and glycolysis of GC cells in vitro and in vivo by using colony formation, CCK-8 assays, Transwell chamber assays, cell scratch assays, and cell-derived xenograft. Furthermore, we examined the molecular processes by which USP31 influences the biological development of GC.</p><p><strong>Results: </strong>Patients with high USP31 expression have a poor prognosis because USP31 is abundantly expressed in GC. Therefore, USP31 reduces the level of ubiquitination of the Wnt/β-catenin pathway by binding to β-catenin, thereby activating glycolysis, which ultimately promotes GC proliferation and aggressive metastasis.</p><p><strong>Conclusion: </strong>USP31 inhibits ubiquitination of β-catenin by binding to it, stimulates the Wnt/β-- catenin pathway, activates glycolysis, and accelerates the biology of GCs, which are all demonstrated in this work.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Recent patents on anti-cancer drug discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115748928297343240425055552","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Gastric cancer (GC) has a poor prognosis because it is highly aggressive, yet there are currently few effective therapies available. Although protein ubiquitination has been shown to play a complex role in the development of gastric cancer, to date, no efficient ubiquitinating enzymes have been identified as treatment targets for GC.

Methods: The TCGA database was used for bioinformatic investigation of ubiquitin-specific protease 31 (USP31) expression in GC, and experimental techniques, including Western blotting, qRT-PCR, and immunohistochemistry, were used to confirm the findings. We also analyzed the relationship between USP31 expression and clinical prognosis in patients with GC. We further investigated the effects of USP31 on the proliferation, invasion, migration, and glycolysis of GC cells in vitro and in vivo by using colony formation, CCK-8 assays, Transwell chamber assays, cell scratch assays, and cell-derived xenograft. Furthermore, we examined the molecular processes by which USP31 influences the biological development of GC.

Results: Patients with high USP31 expression have a poor prognosis because USP31 is abundantly expressed in GC. Therefore, USP31 reduces the level of ubiquitination of the Wnt/β-catenin pathway by binding to β-catenin, thereby activating glycolysis, which ultimately promotes GC proliferation and aggressive metastasis.

Conclusion: USP31 inhibits ubiquitination of β-catenin by binding to it, stimulates the Wnt/β-- catenin pathway, activates glycolysis, and accelerates the biology of GCs, which are all demonstrated in this work.

USP31 激活 Wnt/β-catenin 信号通路并促进胃癌细胞增殖、侵袭和迁移
背景:胃癌(GC)具有高度侵袭性,因此预后较差,但目前几乎没有有效的治疗方法。尽管蛋白质泛素化被证明在胃癌的发展过程中起着复杂的作用,但迄今为止,还没有发现高效的泛素化酶可作为胃癌的治疗靶点:方法:利用 TCGA 数据库对泛素特异性蛋白酶 31(USP31)在 GC 中的表达进行生物信息学调查,并利用 Western 印迹、qRT-PCR 和免疫组化等实验技术确认调查结果。我们还分析了 USP31 表达与 GC 患者临床预后之间的关系。我们通过菌落形成、CCK-8 试验、Transwell 室试验、细胞划痕试验和细胞衍生异种移植,进一步研究了 USP31 对 GC 细胞在体外和体内的增殖、侵袭、迁移和糖酵解的影响。此外,我们还研究了 USP31 影响 GC 生物发展的分子过程:结果:USP31 高表达的患者预后较差,因为 USP31 在 GC 中大量表达。因此,USP31通过与β-catenin结合,降低Wnt/β-catenin通路的泛素化水平,从而激活糖酵解,最终促进GC增殖和侵袭性转移:USP31通过与β-catenin结合抑制其泛素化,刺激Wnt/β-catenin通路,激活糖酵解,加速GCs的生物学进程,这些都在本研究中得到了证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信