NUSAP1 regulates basal cell carcinoma migration, invasion and DNA damage through activation of the Hedgehog signaling pathway

Physiol Int. 2023 May 17;110(2):160-172. doi: 10.1556/2060.2023.00227. Print 2023 Jun 12.

Abstract

Background: Basal cell carcinoma (BCC) is a prevalent cutaneous cancer with an increasing incidence. Nucleolar and spindle associated protein 1 (NUSAP1) is a cell proliferation-related protein that participates in the development of various cancers. However, its role and mechanism in BCC remain elusive.

Methods: The expression of NUSAP1 was detected by western blot. Gain- and loss-of-function assays were performed through the transfection of overexpression plasmid of NUSAP1 and si NUSAP1 into TE354.T cells. The role and mechanism of action of NUSAP1 in BCC were explored by cell counting kit-8 (CCK-8), colony formation, transwell, flow cytometry and western blot assays.

Results: NUSAP1 was highly expressed in TE354.T cells. Overexpression of NUSAP1 enhanced cell viability, colony forming numbers, numbers of migrated and invasive cells and the relative protein expression of RAD51, but reduced the apoptosis rate and the relative protein expression of γH2AX in TE354.T cells. Inverse results were obtained in these indicators after TE354.T cells were downregulated with NUSAP1. Moreover, the relative expression of proteins involved in the Hedgehog signaling pathway was increased by transfection of the overexpression plasmid of NUSAP1 into TE354.T cells, but decreased by the transfection of si NUSAP1 into TE354.T cells.

Conclusion: Both gain- and loss-of-function results revealed that NUSAP1 promoted proliferation, migration and invasion but attenuated apoptosis and DNA damage in BCC, which was involved in the activation of the Hedgehog signaling pathway.

Keywords: DNA damage; NUSAP1; basal cell carcinoma; hedgehog; invasion; migration.

MeSH terms

  • Carcinoma, Basal Cell*
  • Cell Line, Tumor
  • Cell Movement
  • DNA Damage
  • Hedgehog Proteins* / genetics
  • Humans
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Neoplasm Invasiveness

Substances

  • Hedgehog Proteins
  • Microtubule-Associated Proteins
  • NUSAP1 protein, human