Xiang Yun, Cheng Xi, Li Hong, Xu Wenjing, Zhang Weiqiang
Department of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
Reprod Sci. 2025 Apr;32(4):1003-1012. doi: 10.1007/s43032-024-01719-0. Epub 2024 Oct 25.
It is urgent to develop new therapeutic strategies for ovarian cancer (OC). Long-noncoding RNAs (lncRNAs) have participated in multiple biological processes including tumor recurrence and progression. This study aimed to determine the effects and potential regulatory mechanism of lncRNA FOXD2-AS1 in OC progression. Levels of lncRNA FOXD2-AS1 and miR-324-3p in OC tissues and cell lines were analyzed using quantitative real-time PCR (qRT-PCR). The direct target between FOXD2-AS1 or miR-324-3p was determined using bioinformatics tools and further verified by dual-luciferase reporter assay. Cell viability, apoptosis, migration, along invasion were assessed by MTT, flow cytometry, as well as Transwell assays, respectively. In addition, the levels of miR-324-3p, PCNA, MMP9, Bax, Bcl-2, and SOX4 in OC cells were evaluated using qRT-PCR and western blot assays. We observed that lncRNA FOXD2-AS1 was up-regulated while miR-324-3p was down-regulated in OC tissues and cell lines, especially in SKOV3 cells. Moreover, miR-324-3p was a direct target of lncRNA FOXD2-AS1. Meanwhile, SOX4 interacted with miR-324-3p and was negatively regulated by miR-324-3p in SKOV3 cells. Function assays confirmed that lncRNA FOXD2-AS1 silenced depressed cell proliferation, migration, and invasion while accelerating apoptosis. These functions of lncRNA FOXD2-AS1 were attenuated by miR-324-3p inhibition. Our research demonstrated that FOXD2-AS1 silencing restrained cell growth and metastasis of OC via regulating miR-324-3p/SOX4 axis, indicating that lncRNA FOXD2-AS1 could be a novel potential therapeutic target for OC.
开发卵巢癌（OC）的新治疗策略迫在眉睫。长链非编码RNA（lncRNAs）参与了包括肿瘤复发和进展在内的多个生物学过程。本研究旨在确定lncRNA FOXD2-AS1在OC进展中的作用及潜在调控机制。采用定量实时PCR（qRT-PCR）分析OC组织和细胞系中lncRNA FOXD2-AS1和miR-324-3p的水平。使用生物信息学工具确定FOXD2-AS1或miR-324-3p之间的直接靶点，并通过双荧光素酶报告基因检测进一步验证。分别通过MTT、流式细胞术以及Transwell实验评估细胞活力、凋亡、迁移和侵袭。此外，使用qRT-PCR和蛋白质免疫印迹实验评估OC细胞中miR-324-3p、PCNA、MMP9、Bax、Bcl-2和SOX4的水平。我们观察到lncRNA FOXD2-AS1在OC组织和细胞系中上调，而miR-324-3p下调，尤其是在SKOV3细胞中。此外，miR-324-3p是lncRNA FOXD2-AS1的直接靶点。同时，SOX4与miR-324-3p相互作用，并在SKOV3细胞中受到miR-324-3p的负调控。功能实验证实，lncRNA FOXD2-AS1沉默可抑制细胞增殖、迁移和侵袭，同时加速细胞凋亡。lncRNA FOXD2-AS1的这些功能因miR-324-3p抑制而减弱。我们的研究表明，FOXD2-AS1沉默通过调节miR-324-3p/SOX4轴抑制OC细胞的生长和转移，表明lncRNA FOXD2-AS1可能是OC的一个新的潜在治疗靶点。
