FOXA1 co-activates circODC1 and ODC1 in HPV-positive cervical cancer cell growth.

IF 2.1 4区 医学 Q3 ANDROLOGY Systems Biology in Reproductive Medicine Pub Date : 2024-12-01 Epub Date: 2024-05-14 DOI:10.1080/19396368.2024.2311639
Rong Jin, Hongfang Li, Shoushan Nan, Huiju Wang
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Abstract

As demonstrated in previous research, hsa_circ_0052602 (circODC1) is dynamically expressed in HPV-positive cervical cancer (CC). CircODC1 expression was quantified using qRT-PCR, and its role in CC cell growth was assessed via loss-of-function assays. Interactions between miR-607 and circODC1 or ODC1 were confirmed using bioinformatics and mechanistic assays. The association of FOXA1 with the circODC1 promoter was validated through ChIP and luciferase reporter assays. CircODC1 was highly expressed in HPV-positive CC cell lines, and its depletion significantly impeded malignant processes such as proliferation, migration, and invasion. We found that ODC1 also played an oncogenic role in HPV-positive CC cells. CircODC1 was shown to positively regulate ODC1 as a ceRNA, competitively binding to miR-607 to counteract its suppression of ODC1. HPV-associated FOXA1 was identified as a potential transcription factor of circODC1. Restoration experiments showed that overexpression of circODC1 could counterbalance the inhibitory effect of FOXA1 knockdown. These findings offer new insights into therapeutic strategies for HPV-positive CC patients.

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FOXA1 在 HPV 阳性宫颈癌细胞生长过程中共同激活 circODC1 和 ODC1。
之前的研究表明,hsa_circ_0052602(circODC1)在HPV阳性宫颈癌(CC)中动态表达。利用 qRT-PCR 对 circODC1 的表达进行了量化,并通过功能缺失试验评估了它在 CC 细胞生长中的作用。利用生物信息学和机理实验证实了 miR-607 与 circODC1 或 ODC1 之间的相互作用。通过 ChIP 和荧光素酶报告实验验证了 FOXA1 与 circODC1 启动子的关联。CircODC1在HPV阳性的CC细胞系中高表达,它的缺失显著阻碍了增殖、迁移和侵袭等恶性过程。我们发现 ODC1 在 HPV 阳性 CC 细胞中也起着致癌作用。研究表明,CircODC1作为一种ceRNA对ODC1进行正向调节,与miR-607竞争性结合,抵消其对ODC1的抑制作用。HPV相关的FOXA1被鉴定为circODC1的潜在转录因子。恢复实验表明,过表达 circODC1 可以抵消 FOXA1 敲除的抑制作用。这些发现为HPV阳性CC患者的治疗策略提供了新的思路。
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来源期刊
CiteScore
4.30
自引率
4.20%
发文量
27
审稿时长
>12 weeks
期刊介绍: Systems Biology in Reproductive Medicine, SBiRM, publishes Research Articles, Communications, Applications Notes that include protocols a Clinical Corner that includes case reports, Review Articles and Hypotheses and Letters to the Editor on human and animal reproduction. The journal will highlight the use of systems approaches including genomic, cellular, proteomic, metabolomic, bioinformatic, molecular, and biochemical, to address fundamental questions in reproductive biology, reproductive medicine, and translational research. The journal publishes research involving human and animal gametes, stem cells, developmental biology and toxicology, and clinical care in reproductive medicine. Specific areas of interest to the journal include: male factor infertility and germ cell biology, reproductive technologies (gamete micro-manipulation and cryopreservation, in vitro fertilization/embryo transfer (IVF/ET) and contraception. Research that is directed towards developing new or enhanced technologies for clinical medicine or scientific research in reproduction is of significant interest to the journal.
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