Transcription Factor ELF3 Promotes Cervical Cancer Progression via Transcriptional Upregulation of GMPS.

Abstract

Cervical cancer (CC) is one of the most common gynecological malignancies. Although E74-like factor 3 (ELF3) has been implicated as an oncogenic driver in multiple cancers, its expression pattern and functional role in CC remain unclear. An integrated analysis of transcriptome, proteome, and transcription-factor libraries was performed to identify the most significantly upregulated gene in CC, and GEPIA3.0 was used to confirm ELF3 overexpression. The expression levels of ELF3, guanosine monophosphate synthetase (GMPS), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4), as well as the knockdown efficiencies of ELF3 and GMPS, were evaluated by RT-qPCR and Western blot. The effects of ELF3 or GMPS silencing on proliferation, migration, apoptosis, and ferroptosis were assessed by colony-formation, Transwell, and flow cytometry assays. Direct targeting of GMPS by ELF3 was verified by chromatin immunoprecipitation and dual-luciferase reporter assays, and a xenograft model in nude mice was established to demonstrate that ELF3 depletion suppresses CC growth. ELF3 was identified as the most significantly upregulated gene in CC. Silencing either ELF3 or GMPS inhibited proliferation and migration while inducing ferroptosis. Mechanistically, ELF3 transcriptionally regulated GMPS, and GMPS overexpression fully rescued the effects of ELF3 knockdown. In vivo, ELF3 depletion markedly restrained CC xenograft growth. These findings demonstrate that ELF3 functions as an oncogenic transcription factor in CC by upregulating GMPS, thereby enhancing proliferation and migration and restraining ferroptosis. Targeting the ELF3/GMPS axis represents a promising therapeutic strategy for CC.