长非编码 RNA FOXD2-AS1 沉默通过 miR-324-3p/SOX4 信号轴抑制卵巢癌细胞的恶性行为

IF 2.6 3区 医学 Q2 OBSTETRICS & GYNECOLOGY Reproductive Sciences Pub Date : 2024-10-25 DOI:10.1007/s43032-024-01719-0
Yun Xiang, Xi Cheng, Hong Li, Wenjing Xu, Weiqiang Zhang
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引用次数: 0

摘要

开发治疗卵巢癌(OC)的新策略迫在眉睫。长非编码 RNA(lncRNA)参与了包括肿瘤复发和进展在内的多种生物学过程。本研究旨在确定lncRNA FOXD2-AS1在OC进展中的作用和潜在调控机制。研究采用实时定量 PCR(qRT-PCR)技术分析了 OC 组织和细胞系中 lncRNA FOXD2-AS1 和 miR-324-3p 的水平。利用生物信息学工具确定了FOXD2-AS1或miR-324-3p的直接靶点,并通过双荧光素酶报告实验进一步验证了这一结果。细胞活力、凋亡、迁移和侵袭分别通过 MTT、流式细胞术和 Transwell 试验进行了评估。此外,我们还利用 qRT-PCR 和 Western 印迹法评估了 OC 细胞中 miR-324-3p、PCNA、MMP9、Bax、Bcl-2 和 SOX4 的水平。我们观察到,在OC组织和细胞系中,尤其是在SKOV3细胞中,lncRNA FOXD2-AS1上调,而miR-324-3p下调。此外,miR-324-3p 是 lncRNA FOXD2-AS1 的直接靶标。同时,在SKOV3细胞中,SOX4与miR-324-3p相互作用,并受到miR-324-3p的负调控。功能检测证实,沉默的lncRNA FOXD2-AS1能抑制细胞增殖、迁移和侵袭,同时加速细胞凋亡。抑制miR-324-3p会减弱lncRNA FOXD2-AS1的这些功能。我们的研究表明,沉默FOXD2-AS1可通过调节miR-324-3p/SOX4轴抑制OC的细胞生长和转移,这表明lncRNA FOXD2-AS1可能是OC的一个新的潜在治疗靶点。
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Long Non-coding RNA FOXD2-AS1 Silencing Inhibits Malignant Behaviors of Ovarian Cancer Cells Via miR-324-3p/SOX4 Signaling Axis.

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.

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来源期刊
Reproductive Sciences
Reproductive Sciences 医学-妇产科学
CiteScore
5.50
自引率
3.40%
发文量
322
审稿时长
4-8 weeks
期刊介绍: Reproductive Sciences (RS) is a peer-reviewed, monthly journal publishing original research and reviews in obstetrics and gynecology. RS is multi-disciplinary and includes research in basic reproductive biology and medicine, maternal-fetal medicine, obstetrics, gynecology, reproductive endocrinology, urogynecology, fertility/infertility, embryology, gynecologic/reproductive oncology, developmental biology, stem cell research, molecular/cellular biology and other related fields.
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