CircNUP98 通过 miR-520f-3p/ELK4 轴促进胶质瘤细胞的恶性行为。

IF 1.7 4区 医学 Q3 DEVELOPMENTAL BIOLOGY
Liangqin Nie, Tianyu Jiang
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引用次数: 0

摘要

胶质瘤是一种可怕的脑癌,给治疗和预后带来了巨大挑战。环状 RNA 核蛋白 98(circNUP98)已成为多种癌症的潜在调控因子,但它在胶质瘤中的作用仍不清楚。在这里,我们阐明了 circNUP98 在胶质瘤细胞增殖、侵袭和迁移中的功能作用,并揭示了其治疗意义。对胶质瘤细胞进行 si-NUP98 转染,然后评估细胞活力、增殖、侵袭和迁移。测定了 circNUP98 的亚细胞定位,并确定了其下游靶标。我们确定了 circNUP98 与 microRNA (miR)-520f-3p 之间的结合关系,以及 miR-520f-3p 与 ETS 转录因子 ELK4 (ELK4) 之间的结合关系。我们对circNUP98/miR-520f-3p/ELK4的表达水平进行了量化。我们的研究结果表明,circNUP98在胶质瘤细胞中上调,抑制它能显著减少胶质瘤细胞的增殖、侵袭和迁移。从机理上讲,circNUP98可作为miR-520f-3p的海绵,从而缓解miR-520f-3p对ELK4的抑制作用。此外,抑制miR-520f-3p或过表达ELK4可部分缓解circNUP98敲除对胶质瘤细胞行为的抑制作用。总之,我们的研究揭示了circNUP98通过miR-520f-3p/ELK4轴促进胶质瘤细胞的进展,为circNUP98在胶质瘤治疗中的靶向治疗提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CircNUP98 promotes the malignant behavior of glioma cells through the miR-520f-3p/ELK4 axis

Glioma, a formidable form of brain cancer, poses significant challenges in terms of treatment and prognosis. Circular RNA nucleoporin 98 (circNUP98) has emerged as a potential regulator in various cancers, yet its role in glioma remains unclear. Here, we elucidate the functional role of circNUP98 in glioma cell proliferation, invasion, and migration, shedding light on its therapeutic implications. Glioma cells were subjected to si-NUP98 transfection, followed by assessments of cell viability, proliferation, invasion, and migration. Subcellular localization of circNUP98 was determined, and its downstream targets were identified. We delineated the binding relationships between circNUP98 and microRNA (miR)-520f-3p, as well as between miR-520f-3p and ETS transcription factor ELK4 (ELK4). The expression levels of circNUP98/miR-520f-3p/ELK4 were quantified. Our findings demonstrated that circNUP98 was upregulated in glioma cells, and its inhibition significantly attenuated glioma cell proliferation, invasion, and migration. Mechanistically, circNUP98 functioned as a sponge for miR-520f-3p, thereby relieving the inhibitory effect of miR-520f-3p on ELK4. Moreover, inhibition of miR-520f-3p or overexpression of ELK4 partially rescued the suppressive effect of circNUP98 knockdown on glioma cell behaviors. In summary, our study unveils that circNUP98 promotes glioma cell progression via the miR-520f-3p/ELK4 axis, offering novel insights into the therapeutic targeting of circNUP98 in glioma treatment.

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来源期刊
CiteScore
3.30
自引率
5.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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