MEOX2 mediates cisplatin resistance in ovarian cancer via E2F target and DNA repair pathways

J Ovarian Res. 2025 Mar 21;18(1):58. doi: 10.1186/s13048-025-01641-2.

Abstract

Ovarian cancer (OV) is a leading cause of cancer-related mortality among women worldwide. Despite the success of platinum-based chemotherapy in treating OV, the emergence of cisplatin resistance has significantly compromised its therapeutic efficacy. Therefore, understanding the mechanisms underlying cisplatin resistance and its molecular regulation is crucial for improving patient outcomes. This study, MEOX2 was identified as a key gene significantly associated with prognosis and cisplatin resistance in OV through bioinformatics analysis. Its expression level and biological functions were validated using online databases, tissue microarrays, and cellular experiments. The results demonstrated that high MEOX2 expression was closely associated with poor survival outcomes in OV patients, while its expression was significantly reduced in cisplatin-resistant cells. Further gene silencing experiments revealed that silencing MEOX2 markedly enhanced cisplatin resistance in resistant cells and significantly reduced cisplatin-induced early apoptosis, although it had no notable effect on cell proliferation. Moreover, the study showed that MEOX2 was not associated with immune cell infiltration in OV but was positively correlated with angiogenesis-related genes. In cisplatin-resistant cells, gene set enrichment analysis of MEOX2 co-expressed genes highlighted the activation of the E2F target and DNA repair pathway. Additionally, MEOX2 exhibited a significant negative correlation with the MCM protein family. In summary, MEOX2 is highly expressed in OV and is associated with poor patient prognosis. It may confer cisplatin resistance to OV cells by activating the E2F target and DNA repair pathway to mitigate cisplatin-induced early apoptosis. Despite certain limitations, these findings provide novel insights into the potential role of MEOX2 as a prognostic biomarker and therapeutic target in OV.

Keywords: Cisplatin resistance; MEOX2; Ovarian cancer; Prognosis; Transcriptomic analysis.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cisplatin* / pharmacology
  • Cisplatin* / therapeutic use
  • DNA Repair*
  • Drug Resistance, Neoplasm* / genetics
  • E2F Transcription Factors / genetics
  • E2F Transcription Factors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Prognosis

Substances

  • Cisplatin
  • MEOX2 protein, human
  • Homeodomain Proteins
  • E2F Transcription Factors
  • Antineoplastic Agents