OncoTargets and Therapy (Jan 2020)

Nucleolar and Spindle Associated Protein 1 (NUSAP1) Promotes Bladder Cancer Progression Through the TGF-β Signaling Pathway

  • Gao S,
  • Yin H,
  • Tong H,
  • Zhan K,
  • Yang G,
  • Hossain MA,
  • Li T,
  • Gou X,
  • He W

Journal volume & issue
Vol. Volume 13
pp. 813 – 825

Abstract

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Shun Gao, 1, 2 Hubin Yin, 1, 3 Hang Tong, 1, 2 Kai Zhan, 1, 2 Guang Yang, 1, 2 Mohammad Arman Hossain, 1 Tinghao Li, 1, 2 Xin Gou, 1 Weiyang He 1 1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Central Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Weiyang HeDepartment of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong, Chongqing 400016, People’s Republic of ChinaEmail [email protected]: NUSAP1 has been reported to be involved in the progression of several types of cancer. However, its expression and exact role in bladder cancer (BLCA) remains elusive. The aim of this study was to determine the expression and role of NUSAP1 in BLCA.Methods: Tissue microarray, real-time PCR, Western blot and immunohistochemistry assays were carried out to determine NUSAP1 expression in BLCA tissues and cells. The biological roles of NUSAP1 were investigated using CCK-8, EdU labeling, flow cytometry, Transwell, and wound healing assays. Additionally, the effect of NUSAP1 on epithelial-mesenchymal transition (EMT) was investigated by Western blotting and real-time PCR.Results: We found that NUSAP1 was upregulated in BLCA, and its expression was closely related to the poor prognosis of patients. Subsequently, we transfected 5637 and T24 cell lines with NUSAP1 siRNA and an NUSAP1 overexpression plasmid, respectively. NUSAP1 downregulation in 5637 cells inhibited cell proliferation, migration, and invasiveness and enhanced chemosensitivity to gemcitabine, while NUSAP1 overexpression in T24 cells resulted in the inverse effects. Moreover, NUSAP1 regulated EMT via the TGF-β signaling pathway, and when TGF-beta receptor 1 (TGFBR1) was inhibited with the inhibitor SB525334, the invasion and metastasis ability of BLCA cells was significantly suppressed, as well as p-Smad2/3 and vimentin expression.Conclusion: Our above data demonstrate that NUSAP1 contributes to BLCA progression via the TGF-β signaling pathway.Keywords: NUSAP1, bladder cancer, tumor progression, epithelial-mesenchymal transition, TGF-β signaling pathway

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