USP43过表达通过ZEB1激活ERK1/2诱导宫颈癌的生长和干细胞样特性

IF 0.5 4区 医学 Q4 OBSTETRICS & GYNECOLOGY
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引用次数: 0

摘要

宫颈癌(Cervical cancer, CC)是女性最常见的妇科恶性肿瘤类型,靶向干细胞并抑制CC的肿瘤干细胞样特性仍是一个重要的研究领域,旨在改善治疗效果。这项研究聚焦于泛素特异性加工蛋白酶43 (USP43),它是去泛素酶(DUBs)家族的一员,已知在肿瘤进展中起作用,对癌症基因组图谱(TCGA)数据和生存计算的分析显示,USP43在CC中高表达,并与不良预后相关。然而,USP43在CC中的作用报道不足,其潜在机制尚不清楚。为了研究USP43在CC细胞和组织中的作用和机制,我们检测了USP43在CC细胞和组织中的表达,结果显示USP43明显上调。随后,敲低实验表明,降低USP43的表达抑制了CC细胞的增殖,而耗尽USP43则抑制了CC细胞的干细胞样特性并损害了其迁移能力。进一步的研究表明,USP43促进了锌指E-box结合蛋白1 (ZEB1)诱导的CC细胞外调节激酶1/2 (ERK1/2)信号的激活,基于这些发现,我们提出USP43可能是CC的一个有希望的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Overexpression of USP43 induces the growth and stem cell-like properties of cervical cancer by activating ERK1/2 through ZEB1
Cervical cancer (CC) is the most common type of gynecological malignancy in women, and targeting stem cells and inhibiting tumor stem cell-like properties of CC remains an important field of research as an attempt to improve treatment outcomes. This study focused on Ubiquitin-specific-processing Protease 43 (USP43), a member of the deubiquitinase (DUBs) family known to play a role in tumor progression, and analysis of the The Cancer Genome Atlas (TCGA) data and survival computations revealed that USP43 was highly expressed in CC and correlated with poor prognosis. However, the role of USP43 in CC has been under-reported, and its underlying mechanism remains unclear. To investigate the effect and mechanism of USP43, its expression in CC cells and tissues were examined, and the results showed that it was significantly upregulated. Subsequently, knockdown experiments revealed that reducing USP43 expression suppressed CC cell proliferation, and depleting USP43 inhibited the stem cell-like properties of CC cells and impaired their migration abilities. Further investigations indicated that USP43 promoted Zinc finger E-box binding protein 1 (ZEB1)-induced activation of Extracellular regulatory kinase 1/2 (ERK1/2) signaling in CC. Based on these findings, we propose that USP43 could serve as a promising target for CC.
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来源期刊
自引率
25.00%
发文量
58
审稿时长
1 months
期刊介绍: EJGO is dedicated to publishing editorial articles in the Distinguished Expert Series and original research papers, case reports, letters to the Editor, book reviews, and newsletters. The Journal was founded in 1980 the second gynaecologic oncology hyperspecialization Journal in the world. Its aim is the diffusion of scientific, clinical and practical progress, and knowledge in female neoplastic diseases in an interdisciplinary approach among gynaecologists, oncologists, radiotherapists, surgeons, chemotherapists, pathologists, epidemiologists, and so on.
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