关键词: CircNUP98 ELK4 cell invasion cell migration cell proliferation glioma miR‐520f‐3p

来  源:   DOI:10.1002/jdn.10355

Abstract:
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.
摘要:
胶质瘤,一种可怕的脑癌,在治疗和预后方面提出了重大挑战。环状RNA核孔蛋白98(circronneroporin98)已成为各种癌症的潜在调节因子,然而其在神经胶质瘤中的作用尚不清楚.这里,我们阐明了circNUP98在神经胶质瘤细胞增殖中的功能作用,入侵,和移民,阐明其治疗意义。胶质瘤细胞进行si-NUP98转染,然后评估细胞活力,扩散,入侵,和移民。确定了circNUP98的亚细胞定位,并确定了其下游目标。我们描述了circNUP98和microRNA(miR)-520f-3p之间的结合关系,以及miR-520f-3p与ETS转录因子ELK4(ELK4)之间的关系。定量circNUP98/miR-520f-3p/ELK4的表达水平。我们的发现表明,circNUP98在神经胶质瘤细胞中上调,其抑制作用显著减弱神经胶质瘤细胞增殖,入侵,和移民。机械上,circNUP98充当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部分挽救了circNUP98敲低对神经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轴促进神经胶质瘤细胞的进展,为circNUP98在神经胶质瘤治疗中的治疗靶向提供新的见解。
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