Wang Jie, Fang Xinjian, Xing Yajun, Ding Meiqing, Zhu Liangxue, Wang Mingyun
Department of Oncology, Gaochun People's Hospital Affiliated to Jiangsu Health Vocational College, No. 53, Maoshan Road, Gaochun Economic Development Zone, Nanjing, 211306 Jiangsu People's Republic of China.
Cytotechnology. 2025 Feb;77(1):10. doi: 10.1007/s10616-024-00671-w. Epub 2024 Dec 1.
Lysine-specific histone demethylase 1A (KDM1A) has emerged as an attractive therapeutic target for treating various cancers, owing to its observed overexpression. However, its function in epithelial ovarian cancer (EOC) remains uncertain. The current study sought to investigate the function of KDM1A on malignant phenotypes of EOC cells as well as the underlying mechanism. Colony formation assay, cell counting kit-8, wound healing, Transwell assays, and TUNEL assays were performed to investigate the effects of KDM1A, Zinc finger protein 64 (ZFP64), and centromere protein L (CENPL) in vitro, while subcutaneous tumor formation models were established in nude mice to evaluate their roles in vivo. KDM1A, ZFP64, and CENPL were overexpressed in EOC tissues and cells. Knockdown of KDM1A, ZFP64, or CENPL inhibited the biological behavior of EOC cells. In addition, chromatin immunoprecipitation showed that KDM1A stimulated ZFP64 expression by removing the H3K9me2 mark from its promoter. Restoration of ZFP64 promoted EOC cell malignant phenotype in the presence of KDM1A knockdown. ZFP64 activated CENPL transcription. Reactivation of CENPL promoted the growth of EOC cells in vivo inhibited by knockdown of ZFP64. Collectively, KDM1A promoted EOC cell proliferation, migration, and invasion, and reduced apoptosis by activating the ZFP64/CENPL axis, which triggered EOC progression.
The online version contains supplementary material available at 10.1007/s10616-024-00671-w.
赖氨酸特异性组蛋白去甲基化酶1A（KDM1A）因其过表达而成为治疗多种癌症的有吸引力的治疗靶点。然而，其在上皮性卵巢癌（EOC）中的功能仍不确定。本研究旨在探讨KDM1A对EOC细胞恶性表型的作用及其潜在机制。进行集落形成试验、细胞计数试剂盒-8、伤口愈合试验、Transwell试验和TUNEL试验以研究KDM1A、锌指蛋白64（ZFP64）和着丝粒蛋白L（CENPL）在体外的作用，同时在裸鼠中建立皮下肿瘤形成模型以评估它们在体内的作用。KDM1A、ZFP64和CENPL在EOC组织和细胞中过表达。敲低KDM1A、ZFP64或CENPL可抑制EOC细胞的生物学行为。此外，染色质免疫沉淀表明，KDM1A通过从ZFP64启动子上去除H3K9me2标记来刺激其表达。在KDM1A敲低的情况下，ZFP64的恢复促进了EOC细胞的恶性表型。ZFP64激活CENPL转录。CENPL的重新激活促进了体内受ZFP64敲低抑制的EOC细胞的生长。总的来说，KDM1A通过激活ZFP64/CENPL轴促进EOC细胞增殖、迁移和侵袭，并减少细胞凋亡，从而引发EOC进展。
在线版本包含可在10.1007/s10616-024-00671-w获取的补充材料。
