Multi-omics analysis reveals the impact of YAP/TEAD4-mediated EIF5A1 expression on mitochondrial apoptosis and bladder cancer progression

BMC Cancer. 2025 Feb 11;25(1):234. doi: 10.1186/s12885-025-13522-4.

Abstract

Background: Eukaryotic Initiation Factor 5A1 (EIF5A1) is a translation factor, and its pro-tumorigenic role has been extensively documented across various cancer types. However, its specific function in bladder cancer (BLCA) remains unclear.

Methods: We integrated proteomics and transcriptomics data with clinical data from BLCA patients to investigate the correlation between EIF5A1 expression and BLCA, as well as its potential clinical applications. Transcriptomic data were employed to explore the downstream signaling pathways regulated by EIF5A1. Furthermore, ChIP analysis and luciferase reporter assays were conducted to identify the upstream transcription factors regulating EIF5A1.

Results: EIF5A1 expression is significantly upregulated in cancer tissues and cells and is strongly associated with poor prognosis. Silencing EIF5A1 in BLCA cells significantly reduced invasiveness, and proliferative capacity. Mechanistic studies identified YAP/TEAD4 as a transcription factor that regulates EIF5A1, influencing mitochondrial-mediated apoptosis by activating the JAK2/STAT3 signaling pathway, thereby promoting BLCA progression.

Conclusion: Our research demonstrates that EIF5A1 is upregulated in BLCA and associated with poor prognosis. We identified TEAD4 as a potential transcriptional regulator of EIF5A1 and showed that EIF5A1 expression is associated with changes in JAK2/STAT3 signaling and mitochondrial apoptosis in BLCA.

Keywords: Bladder cancer; EIF5A1; JAK/STAT; Mitochondrial apoptosis; YAP/TEAD4.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Disease Progression
  • Eukaryotic Translation Initiation Factor 5A
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mitochondria* / metabolism
  • Mitochondria* / pathology
  • Multiomics
  • Muscle Proteins* / genetics
  • Muscle Proteins* / metabolism
  • Peptide Initiation Factors* / genetics
  • Peptide Initiation Factors* / metabolism
  • Prognosis
  • Proteomics / methods
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Signal Transduction
  • TEA Domain Transcription Factors
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Up-Regulation
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / metabolism
  • Urinary Bladder Neoplasms* / mortality
  • Urinary Bladder Neoplasms* / pathology
  • YAP-Signaling Proteins

Substances

  • Eukaryotic Translation Initiation Factor 5A
  • Peptide Initiation Factors
  • Transcription Factors
  • YAP-Signaling Proteins
  • TEAD4 protein, human
  • DNA-Binding Proteins
  • RNA-Binding Proteins
  • TEA Domain Transcription Factors
  • YAP1 protein, human
  • Muscle Proteins
  • Adaptor Proteins, Signal Transducing