SPOP attenuates the proliferation, invasion, and migration of choriocarcinoma JAR cells by promoting KIF23 degradation

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-04-11 DOI:10.1515/oncologie-2023-0595

Chunli Zhou, Yiyu Chen, Hairong Jiang, Chenchen Xia, Xiaohan Yuan, Qiubo Yu

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引用次数: 0

Abstract

Choriocarcinoma is a highly malignant and aggressive trophoblastic tumor. In our previous study, we discovered that the speckle-type POZ protein (SPOP), which recognizes substrates of E3 ubiquitin ligase, plays a crucial role in trophoblast-derived choriocarcinoma cell lines. Therefore, we investigated the correlation between SPOP and the substrate kinesin-like protein KIF23, as well as the role of KIF23 in choriocarcinoma cells. We constructed JAR cells overexpressing SPOP using lentiviral vectors and subsequently screened the related proteins through ubiquitination-modified quantitative proteomic analysis. The relationship between KIF23 and SPOP was determined using western blotting, and CCK-8, plate cloning, flow cytometry, and Transwell assays were used to investigate the effects of KIF23 and SPOP/KIF23. We identified the KIF23 protein and observed that SPOP promoted its degradation. The abundance of KIF23 increased after the addition of the protease inhibitor MG132. KIF23 was highly expressed in choriocarcinoma cells. Compared with JAR cells transfected with NC–small-interfering RNA (siRNA), the proliferation, invasion, migration, and percentage of G0/G1 cells in the KIF23-siRNA group were significantly lower, and the activation of the Akt/GSK3β signaling pathway was markedly attenuated. Additionally, the sh-SPOP+KIF23-siRNA group exhibited significantly inhibited JAR cell proliferation, invasion, and migration, along with clearly attenuated activation of the Akt/GSK3β signaling pathway. SPOP attenuates the proliferation, invasion, and migration of choriocarcinoma JAR cells by promoting KIF23 degradation.

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SPOP 通过促进 KIF23 降解减轻绒毛膜癌 JAR 细胞的增殖、侵袭和迁移

绒毛膜癌是一种高度恶性的侵袭性滋养细胞肿瘤。在之前的研究中，我们发现斑点型 POZ 蛋白（SPOP）能识别 E3 泛素连接酶的底物，在滋养层细胞衍生的绒毛膜癌细胞系中起着至关重要的作用。因此，我们研究了 SPOP 与底物驱动蛋白样蛋白 KIF23 之间的相关性以及 KIF23 在绒毛膜癌细胞中的作用。我们利用慢病毒载体构建了过表达 SPOP 的 JAR 细胞，并通过泛素化修饰的定量蛋白质组分析筛选了相关蛋白。利用Western印迹测定了KIF23和SPOP之间的关系，并使用CCK-8、平板克隆、流式细胞术和Transwell试验研究了KIF23和SPOP/KIF23的作用。我们鉴定了 KIF23 蛋白，并观察到 SPOP 促进了其降解。加入蛋白酶抑制剂 MG132 后，KIF23 的丰度增加。KIF23在绒毛膜癌细胞中高表达。与转染NC-小干扰RNA（siRNA）的JAR细胞相比，KIF23-siRNA组细胞的增殖、侵袭、迁移和G0/G1细胞百分比显著降低，Akt/GSK3β信号通路的激活明显减弱。此外，sh-SPOP+KIF23-siRNA 组的 JAR 细胞增殖、侵袭和迁移明显受到抑制，Akt/GSK3β 信号通路的激活也明显减弱。 SPOP通过促进KIF23降解来抑制绒毛膜癌JAR细胞的增殖、侵袭和迁移。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.