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WSB2在人类肿瘤中致癌作用的泛癌分析。

Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors.

作者信息

Deng Yingzi, Li Yifei, Li Ruobing, Guo Xiaohui, Liu Yan, Wang Shuqing, Zhang Juan, Li Mi, Zhao Lina, Cai Haifeng, Zhang Yunfeng, Hu Fen

机构信息

Department of Bioinformatics, College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China.

Department of Bioinformatics, College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China.

出版信息

Mol Med Rep. 2025 Oct;32(4). doi: 10.3892/mmr.2025.13625. Epub 2025 Jul 25.

Abstract

WD repeat and SOCS box containing 2 (WSB2) is an E3 ubiquitin ligase that might be involved in regulating protein stability, thus performing important roles in the development of different types of cancer. However, the biological significance of WSB2 in pan‑cancer is unclear. Pan‑cancer analysis with the online platforms UALCAN and TIMER2.0. revealed that the expression levels of WSB2 were increased in various types of tumors, including breast invasive carcinoma, uterine corpus endometrial carcinoma, liver hepatocellular carcinoma and were decreased in other types such as colon adenocarcinoma, kidney chromophobe and rectum adenocarcinoma, compared with that in their corresponding normal tissues. In addition, pan‑cancer analysis using The Human Protein Atlas database indicated that WSB2 expression levels vary across different cancer types. Reverse transcription‑quantitative PCR (RT‑qPCR) revealed that WSB2 expression varied in 11 different cell lines. Promoter activity analysis indicates that specificity protein 1 carries out a key role in regulating WSB2 expression by binding to its promoter region. UALCAN and Kaplan‑Meier analysis were used to assess the pathological stage and prognostic value of WSB2 in pan‑cancer. Finally, overexpression of WSB2 promoted the proliferation and migration of MCF‑7 and MDA‑MB‑231 cells. Western blotting revealed that WSB2 increased the levels of vimentin, Snail and ERK1/2, and inhibited the expression of p53 and E‑cadherin in MDA‑MB‑231 and MCF‑7 cells. Transcriptome sequencing analysis identified 118 differentially expressed genes associated with WSB2 overexpression, which were mainly enriched in the 'p53 signaling pathway'. Furthermore, the expression of NUPR1 (encoding nuclear protein 1, transcriptional regulator), LDLRAD4 (encoding low density lipoprotein receptor class A domain containing 4) and MDM2 (encoding mouse double min 2) were verified by RT‑qPCR. Overall, the present study contributes to the understanding of the carcinogenic role of WSB2 in different types of cancer.

摘要

含WD重复序列和SOCS盒蛋白2(WSB2)是一种E3泛素连接酶,可能参与调节蛋白质稳定性,从而在不同类型癌症的发生发展中发挥重要作用。然而,WSB2在泛癌中的生物学意义尚不清楚。利用在线平台UALCAN和TIMER2.0进行泛癌分析。结果显示,与相应正常组织相比,WSB2在多种肿瘤类型中表达水平升高,包括乳腺浸润性癌、子宫内膜癌、肝细胞癌,而在其他类型肿瘤如结肠腺癌、肾嫌色细胞癌和直肠腺癌中表达水平降低。此外,使用人类蛋白质图谱数据库进行的泛癌分析表明,WSB2的表达水平在不同癌症类型中有所差异。逆转录定量PCR(RT-qPCR)显示,WSB2在11种不同细胞系中的表达各不相同。启动子活性分析表明,特异性蛋白1通过结合其启动子区域在调节WSB2表达中起关键作用。利用UALCAN和Kaplan-Meier分析评估WSB2在泛癌中的病理分期和预后价值。最后,WSB2的过表达促进了MCF-7和MDA-MB-231细胞的增殖和迁移。蛋白质免疫印迹分析显示,WSB2增加了MDA-MB-231和MCF-7细胞中波形蛋白、Snail和ERK1/2的水平,并抑制了p53和E-钙黏蛋白的表达。转录组测序分析确定了118个与WSB2过表达相关的差异表达基因,这些基因主要富集在“p53信号通路”中。此外,通过RT-qPCR验证了NUPR1(编码核蛋白1,转录调节因子)、LDLRAD4(编码含A类低密度脂蛋白受体结构域4)和MDM2(编码小鼠双微体2)的表达。总体而言,本研究有助于理解WSB2在不同类型癌症中的致癌作用。

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