Objective  To investigate the role and mechanism of sex-determining region Y-box protein 9 (SOX9) in the progression of ovarian cancer.

Methods  The ovarian cancer cell lines with stable knockdown of SOX9 were constructed. The effects of SOX9 knockdown on the proliferation, invasion and migration abilities of ovarian cancer cell lines were detected by CCK-8 assay, Transwell assay, and cell scratch assay, respectively. The effects of SOX9 knockdown on ferroptosis in ovarian cancer cell lines were evaluated by the level of Fe²⁺, glutathione (GSH), malondialdehyde (MDA), and Western blot analysis. The effects of SOX9 knockdown on the lipid peroxidation level of ovarian cancer cell lines were observed by confocal fluorescence microscopy. Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) was performed to examine the binding of SOX9 to its downstream target gene, SLC7A11.

Results  Knockdown of SOX9 significantly inhibits the proliferation, invasion and migration abilities of ovarian cancer cells. Meanwhile, SOX9 transcriptionally regulates SLC7A11 and activates ferroptosis via the SLC7A11/GPX4 signaling axis.

Conclusion  SOX9 promotes ferroptosis in ovarian cancer cells by regulating the SLC7A11/GPX4 signaling pathway, ultimately inhibiting ovarian cancer progression.

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