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

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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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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author via email request.

Abbreviations

BLCA:

Bladder cancer

Nup:

Nucleoporin

PI3K:

Phosphatidylinositol 3-kinase

JAK/STAT:

Janus kinase/signal transducer and activator of transcription

IHC:

Immunohistochemistry

qRT-PCR:

Quantitative real-time polymerase chain reaction

ALDH:

Aldehyde dehydrogenase

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Author notes

  1. Zhe Wang and Jing Zhang have equal contribution to this study.

Authors and Affiliations

  1. Urology Department, The First Affiliated Hospital of Hebei North University, No. 12, Changqing Road, Zhangjiakou, 050051, Hebei Province, China

    Zhe Wang, Lina Luo, Chao Zhang, Shuo Liu, Huaian Chen & Wenlong Miao

  2. Department of Medical Oncology, The First Affiliated Hospital of Hebei North University, No. 12, Changqing Road, Zhangjiakou, 050051, Hebei Province, China

    Jing Zhang

  3. Medical Department, The First Affiliated Hospital of Hebei North University, No. 12, Changqing Road, Zhangjiakou, 050051, Hebei Province, China

    Xiaomeng Huang

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  1. Zhe Wang
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Contributions

Conception and design: WM, ZW, JZ. Data analysis and interpretation: ZW, JZ, LL, CZ, collection of data: ZW, XH, SL, HC. Manuscript writing: all authors. final approval of manuscript: all authors.

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Correspondence to Wenlong Miao.

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The authors declare that they have no conflict of interest.

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Collection of samples used in this study was approved by the Ethics Committee of The First Affiliated Hospital of Hebei North University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Each animal experimental procedure gained approval from Animal Ethics Committee of The First Affiliated Hospital of Hebei North University. The experimental protocol was performed in accordance with the relevant guidelines and regulations of the Basel Declaration. The study is reported in accordance with ARRIVE guidelines (https://arriveguidelines.org).

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Wang, Z., Zhang, J., Luo, L. et al. Nucleoporin 93 Regulates Cancer Cell Growth and Stemness in Bladder Cancer via Wnt/β-Catenin Signaling. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01184-9

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