Resveratrol regulates ferroptosis and endometrial cancer progression by inhibiting CEBPA-mediated FAM83B expression

Endometrial cancer (EC) is one of the most common gynecologic malignancies. CCAAT enhancer binding protein α (CEBPA) and family with sequence similarity 83, member B (FAM83B) are related to development of multiple cancers. Additionally, resveratrol (Res) exerts anticancer effects in various cancers, yet its role in EC is poorly understood. This research aims to unravel the interactions and molecular mechanisms of CEBPA, FAM83B, and Res in EC progression and ferroptosis. mRNA and protein expression levels were examined using Reverse transcription-quantitative polymerase chain reaction and western blot, respectively. Functional assays were used to assess cell proliferation, apoptosis, angiogenesis ability, and viability. Ferroptosis was evaluated by measuring the levels of malondialdehyde (MDA), iron (Fe2+), superoxide dismutase (SOD) activity, and glutathione (GSH) levels using commercial kits, as well as by analyzing the expression of key ferroptosis-related proteins (GPX4 and SLC7A11) via western blot. The ferroptosis inhibitor Ferrostatin-1 (Fer-1) was used in rescue experiments. The interactions between CEBPA and FAM83B were analyzed using JASPAR website, luciferase reporter assay, and chromatin Immunoprecipitation (CHIP) assays. The binding energy of Res and CEBPA was analyzed using molecular docking. EC xenograft models were constructed to evaluate tumor growth under Res treatment. Immunohistochemistry and western blot assays were used to assess protein expression in tumor tissues. In EC cells, CEBPA expression levels were up-regulated, and silencing CEBPA suppressed EC cell proliferation, HUVEC tube formation, levels of SOD and GSH, and expression of GPX4 and SLC7A11, while promoted cell apoptosis, MDA and Fe 2+ levels. CEBPA down-regulation suppressed FAM83B expression. Notably, Res reduced CEBPA and FAM83B expression. Mechanistically, Res mitigated EC cell malignant behavior and promoted ferroptosis via regulating CEBPA/FAM83B axis. In vivo , Res suppressed tumor growth of EC. Res alleviated EC cell malignant behavior and facilitated ferroptosis via regulating the CEBPA/FAM83B axis.