Yu Guoyu, Wei Fang, Li Wanying, Guo Qiuyun, Zhang Lihong
Department of Oncology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
BMC Cancer. 2025 Aug 9;25(1):1290. doi: 10.1186/s12885-025-14740-6.
Ovarian cancer, a prevalent malignancy with the highest fatality rate among gynecological cancers, continues to face challenges in the development of effectively targeted therapeutic approaches. While the FAM111B gene has been implicated in various cancer types, its specific role in ovarian cancer remains poorly understood.
The ES2 and A2780 ovarian cell lines were exploited to explore the cellular proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in FAM111B knockdown experiments. We constructed a mouse tumor model to investigate the impact of FAM111B silencing in vivo; employed tissue microarray to explore the prognostic value of different FAM111B expression levels; and applied western-blot assay, MYC-overexpression rescue experiments, protein transcriptomics, and bioinformatics analysis to examine the downstream molecular mechanisms underlying FAM111B actions.
Our in vitro experiments indicated that the inhibition of FAM111B resulted in reduced cellular proliferation, migration, invasion, and EMT in ovarian cancer cell lines and in the suppression of tumor growth in a mouse xenograft model. Immunohistochemical analyses conducted on tissue-microarray samples obtained from patients with serous ovarian cancer indicated that elevated levels of FAM111B expression were associated with unfavorable prognostic outcomes. The silencing of FAM111B mechanistically constrained MYC expression, with subsequent MYC overexpression reversing the phenotypic suppression caused by FAM111B silencing. Additionally, protein transcriptomic analysis implicated FAM111B in genetic-information processing via the MYC pathway, underscoring FAM111B's central role in ovarian cancer tumorigenesis.
These findings suggest that FAM111B may serve as a novel biomarker and potential therapeutic target in ovarian cancer.
卵巢癌是一种常见的恶性肿瘤，在妇科癌症中死亡率最高，在有效靶向治疗方法的开发方面仍面临挑战。虽然FAM111B基因已被认为与多种癌症类型有关，但其在卵巢癌中的具体作用仍知之甚少。
利用ES2和A2780卵巢癌细胞系，在FAM111B基因敲低实验中探索细胞增殖、迁移、侵袭和上皮-间质转化（EMT）。我们构建了一个小鼠肿瘤模型，以研究FAM111B基因沉默在体内的影响；采用组织芯片来探索不同FAM111B表达水平的预后价值；并应用蛋白质印迹分析、MYC过表达拯救实验、蛋白质转录组学和生物信息学分析，来研究FAM111B作用的下游分子机制。
我们的体外实验表明，抑制FAM111B可导致卵巢癌细胞系的细胞增殖、迁移、侵袭和EMT减少，并抑制小鼠异种移植模型中的肿瘤生长。对浆液性卵巢癌患者的组织芯片样本进行免疫组化分析表明，FAM111B表达水平升高与不良预后结果相关。FAM111B基因沉默在机制上限制了MYC的表达，随后MYC过表达逆转了FAM111B基因沉默引起的表型抑制。此外，蛋白质转录组分析表明FAM111B通过MYC途径参与遗传信息处理，突出了FAM111B在卵巢癌肿瘤发生中的核心作用。
这些发现表明，FAM111B可能是卵巢癌中的一种新型生物标志物和潜在治疗靶点。
