Overexpression of NuSAP1 is predictive of an unfavourable prognosis and promotes proliferation and invasion of triple-negative breast cancer cells via the Wnt/β-catenin/EMT signalling axis

Gene. 2020 Jul 15:747:144657. doi: 10.1016/j.gene.2020.144657. Epub 2020 Apr 13.

Abstract

Objective: We analysed the effect of expression of nucleolar spindle-associated protein 1 (NuSAP1) on the prognosis of breast cancer (BC) and investigated its potential mechanism of tumourigenicity in triple-negative breast cancer (TNBC) cell lines.

Materials and methods: We downloaded the RNA-seq breast cancer (BC) data from The Cancer Genome Atlas (TCGA) and screened for the NuSAP1 gene using R software. The clinical data for patients with BC were screened and analysed using R software. A survival curve was drawn using the Kaplan-Meier Plotter. Cell proliferation and invasion were verified by the Cell Counting Kit-8 and Transwell assays. Expression of NuSAP1, the Wnt/β-catenin pathway, and epithelial-mesenchymal-transition-related proteins in TNBC was detected using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting (WB).

Results: Expression of NuSAP1 was upregulated in BC. The change in NuSAP1 expression levels was associated with multiple clinicopathological factors, and the higher the expression of NuSAP1 was, the shorter the survival time. In MDA-MB-231 and BT549 cells, knockdown of NuSAP1 expression resulted in a significant decrease in cell proliferation and invasion; a decrease in expression of cyclin D1, vimentin, Slug, Twist, wnt3a, and pβ-catenin; and an increase in expression of e-cadherin. The results of the sh-NuSAP1 + ov-NuSPA1 group were the opposite of the results of the sh-NuSAP1 group.

Conclusion: NuSAP1 is a carcinogen that facilitates progression of TNBC through the Wnt/β-catenin and epithelial-mesenchymal transition pathways.

Keywords: Cell invasion; Cell proliferation; EMT; NuSAP1; Triple-negative breast cancer; Wnt/β-catenin pathway.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Survival Analysis
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*
  • Wnt Signaling Pathway*

Substances

  • Microtubule-Associated Proteins
  • NUSAP1 protein, human
  • RNA, Messenger