SOX9通过调控SLC7A11/GPX4介导的铁死亡抑制卵巢癌进展的机制研究OA
SOX9 promotes ovarian cancer progression through activating ferroptosis via SLC7A11/GPX4 pathway
目的 探索性别决定区Y框蛋白 9(SOX9)在卵巢癌进展中的作用及机制.方法 构建SOX9 稳定敲低的卵巢癌细胞系,通过CCK-8 法、Transwell实验、细胞划痕实验检测细胞增殖、侵袭和迁移能力;通过检测Fe2+、谷胱甘肽、丙二醛水平和Western blot实验评估敲低SOX9 对卵巢癌细胞铁死亡的影响;通过共聚焦荧光显微镜观察敲低SOX9对脂质过氧化水平的影响;通过染色质免疫共沉淀结合定量PCR检测SOX9 与下游靶基因SLC7A11的结合.结果 敲低SOX9 显著抑制卵巢癌细胞的增殖、侵袭和迁移能力,SOX9 通过调控SLC7A11 的转录抑制SLC7A11/GPX4 信号通路,从而激活卵巢癌细胞铁死亡.结论 SOX9 通过调控SLC7A11/GPX4 信号通路促进卵巢癌细胞铁死亡,进而抑制卵巢癌的进展.
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.
叶学均;王中显;李贵香;程大玲;陶杏元
湖北省第三人民医院妇产科(武汉 430060)湖北省第三人民医院妇产科(武汉 430060)湖北省第三人民医院妇产科(武汉 430060)湖北省第三人民医院妇产科(武汉 430060)湖北省第三人民医院妇产科(武汉 430060)
医药卫生
SOX9卵巢癌铁死亡
SOX9Ovarian cancerFerroptosis
《医学新知》 2026 (1)
62-69,8
湖北省自然科学基金(2021CFB576)
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