Highly Expressed Z-DNA Binding Protein 1 in Esophageal Cancer Promotes Tumor Growth

Dig Dis Sci. 2024 May;69(5):1674-1690. doi: 10.1007/s10620-024-08375-z. Epub 2024 Mar 20.

Abstract

Background: Esophageal cancer (ESCA) is a common malignant tumor of the digestive tract, and its poor prognosis is mainly attributed to the occurrence of invasion and metastasis. Z-DNA binding protein 1 (ZBP1), as a mRNA regulatory factor, plays an important role in the occurrence and development of various tumors. However, the role of ZBP1 in ESCA is not yet understood.

Aims: This study aims to explore the expression of ZBP1 in ESCA and its role in the development of ESCA.

Methods: Using bioinformatics analysis and immunohistochemistry staining, we detected the expression of ZBP1 in ESCA and normal tissues. The potential mechanism of ZBP1 in ESCA was analyzed from the aspects of genetic mutations, protein interaction networks, and pathway enrichment. We performed functional experiments in vitro to elucidate the effect of ZBP1 on ESCA cells.

Results: ZBP1 was found to be significantly upregulated in ESCA compared to adjacent noncancerous tissues, and its expression is closely related to gender, age, and lymph node metastasis. In ESCA, the genetic variation rate of ZBP1 is 8%, and its expression is positively correlated with immune cell infiltration. The ZBP1 co-expressed gene is mainly involved in processes such as lymph node proliferation and intercellular adhesion. In vitro experiments have confirmed that downregulation of ZBP1 significantly inhibited the proliferation, migration, and invasion of ESCA cells.

Conclusion: This research proves that downregulation of ZBP1 can inhibit the progression of ESCA. This finding indicates that ZBP1 may be a novel biomarker to improve the diagnosis and treatment of ESCA.

Keywords: Bioinformatics analysis; Esophageal cancer; Invasion; Migration; ZBP1.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Up-Regulation