Bioinformatics and experimental validation of an AURKA/TPX2 axis as a potential target in esophageal squamous cell carcinoma

Oncol Rep. 2023 Jun;49(6):116. doi: 10.3892/or.2023.8553. Epub 2023 Apr 21.

Abstract

Aurora kinase A (AURKA), a serine/threonine kinase that regulates mitotic processes, has garnered significant interest given its association with the development of several types of cancer. In the present study, it was shown that AURKA expression was significantly upregulated in esophageal squamous cell carcinoma (ESCC) and could serve as a diagnostic and prognostic indicator based on data obtained from The Cancer Genome Atlas (TCGA) and immunohistochemical analysis. In addition, AURKA was functionally associated with ESCC cell proliferation and colony formation in vitro and knockdown of AURKA inhibited ESCC tumor growth in vivo. Both bioinformatics analysis and pull‑down assays demonstrated that TPX2 interacted with AURKA, and their expression was correlated. AURKA cooperated with TPX2 to regulate ESCC progression via the PI3K/Akt pathway. Furthermore, AURKA or TPX2 expression levels were negatively associated with the infiltration of cytotoxic cells, CD8+ T cells and mast cells, but positively associated with Th2 cells. The present study provided a relatively comprehensive understanding of the oncogenic roles of AURKA in ESCC based on data obtained from TCGA combined with experimental analysis.

Keywords: AURKA; ESCC; TPX2; bioinformatics; therapeutic target.

MeSH terms

  • Aurora Kinase A
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Computational Biology
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism

Substances

  • Aurora Kinase A
  • Phosphatidylinositol 3-Kinases
  • TPX2 protein, human
  • Microtubule-Associated Proteins
  • Cell Cycle Proteins
  • AURKA protein, human

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant no. 82273058 and 82002592), the Science and Technology Project of Henan Province (grant no. 222102310156), the Doctoral Research Start-up Fund Project of Nanyang Institute of Technology (grant no. NGBJ-2022-05) and the Talent Program of Central China: Science and Technology Innovation Leading Talent (grant no. 234200510006).