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Nucleolar and spindle-associated protein 1 accelerates cellular proliferation and invasion in nasopharyngeal carcinoma by potentiating Wnt/β-catenin signaling via modulation of GSK-3β

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Abstract

Nucleolar and spindle-associated protein 1 (NUSAP1) is a pivotal tumor-related protein that has been implicated in the progression of broad spectrum of tumors. However, no detailed study of the role of NUSAP1 in nasopharyngeal carcinoma (NPC) has been reported. The aim of this work is to enhance our understanding of NUSAP1 in the progression of NPC. By analyzing data available within the Oncomine database, we found that NUSAP1 expression was elevated in NPC relative to normal tissues. Further, we showed that NUSAP1 expression in clinical specimens of NPC and several NPC cell lines was elevated. Down-regulation of NUSAP1 by gene silencing markedly depleted the capacity of NPC cells to proliferate and invade. Contrastingly, overexpression of NUSAP1 potentiated the proliferative and invasive abilities of NPC cells. Further mechanistic research revealed that NUSAP1 knockdown decreased levels of Wnt/β-catenin signaling in NPC cells via a mechanism associated with downregulation of glycogen synthase kinase-3β (GSK-3β) phosphorylation. However, suppression of GSK-3β markedly abolished the inhibitory effect of NUSAP1 knockdown on Wnt/β-catenin signaling. Further, inhibition of Wnt/β-catenin signaling partially reversed NUSAP1-mediated tumor growth in NPC cells. In addition, NUSAP1 knockdown restrained tumorigenesis of NPC in vivo, and was associated with down-regulation of Wnt/β-catenin signaling. In conclusion, these findings demonstrate that NUSAP1 is capable of accelerating proliferation and invasion in NPC cells by potentiating Wnt/β-catenin signaling. Our study unveils a potential role of NUSAP1 in promoting NPC tumors and suggests that the protein is an attractive antitumor target for NPC treatment.

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Data availability

The data and material used to support the findings of this study are available from the corresponding author upon request.

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Authors and Affiliations

  1. Department of Otolaryngology, Xianyang Hospital of Yan’an University, Xianyang City, 712000, Shaanxi Province, China

    Ligang Zhang & Yabin Dang

  2. Department of Otolaryngology, Xianyang First People’s Hospital, 10 Biyuan Road, Xianyang City, 712000, Shaanxi Province, China

    Ying Wang & Xin Fan

Authors
  1. Ligang Zhang
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  2. Yabin Dang
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  3. Ying Wang
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  4. Xin Fan
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Contributions

Ligang Zhang designed the study, performed the experiments and drafted the manuscript. Yabin Dang performed the experiment. Ying Wang analyzed the data. Xin Fan designed the study and reviewed the manuscript.

Corresponding author

Correspondence to Xin Fan.

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The authors declare that they have no conflict of interest.

Ethics approval

The use of clinical specimens for research purposes was approved by Ethics Committee of Xianyang Hospital of Yan’an University, and research procedures were performed in accordance with the Declaration of Helsinki. Animal studies were carried out with the approval of Ethics Committee of Xianyang Hospital of Yan’an University.

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Written informed consent was acquired from each patient.

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Zhang, L., Dang, Y., Wang, Y. et al. Nucleolar and spindle-associated protein 1 accelerates cellular proliferation and invasion in nasopharyngeal carcinoma by potentiating Wnt/β-catenin signaling via modulation of GSK-3β. J Bioenerg Biomembr 52, 441–451 (2020). https://doi.org/10.1007/s10863-020-09860-6

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  • DOI: https://doi.org/10.1007/s10863-020-09860-6

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