Nucleoporin 93 Regulates Cancer Cell Growth and Stemness in Bladder Cancer via Wnt/β-Catenin Signaling.

IF 2.5 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biotechnology Pub Date : 2025-05-01 Epub Date: 2024-05-14 DOI:10.1007/s12033-024-01184-9

Zhe Wang, Jing Zhang, Lina Luo, Chao Zhang, Xiaomeng Huang, Shuo Liu, Huaian Chen, Wenlong Miao

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Abstract

Bladder cancer (BLCA) is a prevalent cancer type with an unmet need for new therapeutic strategies. Nucleoporin 93 (Nup93) is implicated in the pathophysiology of several cancers, but its relationship with bladder cancer remains unclear. Nup93 expression was analyzed in TCGA datasets and 88 BLCA patient samples. Survival analysis and Cox regression models evaluated the association between Nup93 levels and patient prognosis. BLCA cells were used to investigate the effects of Nup93 overexpression or knockdown on cell growth, invasion, stemness (sphere formation and ALDH2 + cancer stem cell marker), and Wnt/β-catenin signaling in vitro. The Wnt activator BML-284 was used to confirm the involvement of Wnt/β-catenin signaling pathway. A xenograft mouse model validated the in vitro findings. Nup93 was highly expressed in BLCA tissues and cell lines, and high Nup93 expression correlated with poor prognosis in BLCA patients. Nup93 silencing inhibited BLCA cell proliferation, Wnt/β-catenin activation, and cancer cell stemness. Conversely, Nup93 overexpression promoted these effects. BML-284 partially rescued the reduction in cell growth and stemness markers caused by Nup93 knockdown. Nup93 knockdown also suppressed the tumor formation of BLCA cells in vivo. Nup93 regulates BLCA cell growth and stemness via the Wnt/β-catenin pathway, suggesting its potential as a prognostic marker and therapeutic target in BLCA.

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核多肽 93 通过 Wnt/β-Catenin 信号调控膀胱癌中癌细胞的生长和干性。

膀胱癌（BLCA）是一种常见的癌症类型，对新治疗策略的需求尚未得到满足。核orin 93（Nup93）与多种癌症的病理生理学有关，但它与膀胱癌的关系仍不清楚。我们在 TCGA 数据集和 88 例膀胱癌患者样本中分析了 Nup93 的表达。生存分析和 Cox 回归模型评估了 Nup93 水平与患者预后之间的关系。研究人员利用BLCA细胞研究了Nup93过表达或敲除对细胞生长、侵袭、干性（球体形成和ALDH2 +癌症干细胞标记）以及体外Wnt/β-catenin信号转导的影响。Wnt 激活剂 BML-284 被用来证实 Wnt/β-catenin 信号通路的参与。异种移植小鼠模型验证了体外研究结果。Nup93在BLCA组织和细胞系中高表达，Nup93的高表达与BLCA患者的不良预后相关。沉默Nup93可抑制BLCA细胞增殖、Wnt/β-catenin激活和癌细胞干性。相反，Nup93过表达则会促进这些效应。BML-284部分缓解了Nup93敲除导致的细胞生长和干性标志物的减少。Nup93敲除还抑制了BLCA细胞在体内形成肿瘤。Nup93通过Wnt/β-catenin通路调节BLCA细胞的生长和干性，这表明它有可能成为BLCA的预后标志物和治疗靶点。

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来源期刊

Molecular Biotechnology 医学-生化与分子生物学

CiteScore

4.10

自引率

3.80%

发文量

165

审稿时长

6 months

期刊介绍： Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.