Zinc fingers and homeoboxes 2 inhibition could suppress the proliferation of ovarian cancer cells by apoptosis pathway

Clin Transl Oncol. 2023 Jul;25(7):2116-2126. doi: 10.1007/s12094-023-03090-z. Epub 2023 Feb 6.

Abstract

Objective: The Zinc fingers and homeoboxes (ZHX) protein family has been reported to be involved in tumor development; however, it remains controversial whether these proteins can act as promoters or inhibitors of cancer development. The current study focused on the biological role of ZHX2 in ovarian cancer.

Methods: Tissue microarrays were established using 154 ovarian cancer samples. Immunohistochemical analysis was employed to determine the expression levels of ZHX2 in ovarian cancer samples. The prognostic analysis was performed using the Kaplan-Meier method and compared with a log-rank test. The specific role of ZHX2 in ovarian cancer was investigated in cell lines in vitro.

Results: It was found that ZHX2 was not significantly overexpressed in ovarian cancer samples; however, its expression was significantly correlated with advanced tumor grade. Patient survival analysis indicated that patients with high expression of ZHX2 exhibited worse overall survival rate compared with those with low expression of ZHX2. Furthermore, univariate and multivariate analyses demonstrated that ZHX2 was an independent prognostic factor of progression-free survival in patients with ovarian cancer. In vitro experiments indicated that inhibition of ZHX2 could significantly suppress ovarian cancer cell proliferation via induction of the apoptotic pathway.

Conclusions: The data indicated that ZHX2 may be considered a promising biomarker in ovarian cancer and that inhibition of its expression may be a potential therapeutic target in ovarian cancer treatment.

Keywords: Apoptosis; Ovarian cancer; Proliferation; ZHX2.

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Female
  • Genes, Homeobox*
  • Homeodomain Proteins* / genetics
  • Humans
  • Ovarian Neoplasms* / drug therapy
  • Transcription Factors* / genetics
  • Zinc Fingers

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • ZHX2 protein, human