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Transcription factor FOXA1 suppresses ferroptosis of cervical cancer cells by upregulating SLC7A11 expression.

Created on 26 Jun 2026

Authors

Fei Gao, Yan Zeng, Li Jia, Jun He, Huarong He

Published in

Cell division. Jun 25, 2026. Epub Jun 25, 2026.

Abstract

Ferroptosis, a unique modality of cell death, possesses critical activity in tumorigenesis. This study defined the role of transcription factor (TF) forkhead box A1 (FOXA1) in modulating ferroptosis of cervical cancer (CC), a prevalent disease with high mortality rates in females. mRNA analysis was done by quantitative real-time PCR (qRT-PCR), and protein expression was analyzed by immunoblotting and immunohistochemistry (IHC). Colony formation and EdU proliferation assays were used to evaluate cell growth. Apoptosis was detected by flow cytometry. The contents of SOD, MDA, GSH, ROS and Fe2+ were measured by assay kits. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase assays were applied to analyzed the binding of FOXA1 to the SLC7A11 promoter. FOXA1 was an overexpressed factor in CC, which was related to prognosis of human CC. FOXA1 downregulation impaired CC cell in vitro proliferation, promoted apoptosis, and induced ferroptosis. FOXA1 was validated to bind to the promoter of SLC7A11 and enhance SLC7A11 transcription. Furthermore, the FOXA1/SLC7A11 cascade affected proliferation, apoptosis and ferroptosis of CC cells. In addition, FOXA1 downregulation impeded the in vivo tumorigenesis of C33A CC cells. Our study has identified FOXA1 as a crucial repressor of CC cell ferroptosis depending on its activation of SLC7A11 transcription. Developing inhibitors of FOXA1 is a promising way of harnessing ferroptosis for CC treatment.

PMID:
42351196
Bibliographic data and abstract were imported from PubMed on 26 Jun 2026.

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