CircYIPF6通过靶向miR-760调节PTBP1表达,调控胶质瘤细胞增殖、凋亡和糖酵解。

IF 1.8 4区 医学 Q4 NEUROSCIENCES Translational Neuroscience Pub Date : 2023-01-01 DOI:10.1515/tnsci-2022-0271
Dan Lei, Wenyong Xiao, Bo Zhang
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摘要

背景:近年来的研究表明,环状rna在肿瘤中作为microRNA海绵调节肿瘤相关基因的表达。在此,我们研究了circYIPF6在胶质瘤中的功能和分子机制。方法:采用5-乙基-2′-脱氧尿苷法、集落形成法和流式细胞术观察胶质瘤细胞的增殖和凋亡情况。糖酵解代谢水平通过测量葡萄糖摄取和乳酸生成来评估。western blot检测Bax、Bcl2、GLUT1、LDHA、PTBP1蛋白水平。双荧光素酶报告基因证实了miR-760与circYIPF6或PTBP1之间的相互作用。通过异种移植实验确定circYIPF6沉默对胶质瘤生长的影响。结果:circYIPF6在胶质瘤中显著上调。敲低circYIPF6抑制胶质瘤细胞增殖和糖酵解,促进细胞凋亡。机制研究表明,circYIPF6靶向miR-760,并能大量海绵miR-760抑制其下游靶基因PTBP1的表达。功能挽救实验表明,miR-760抑制和PTBP1过表达均可减弱circYIPF6沉默对胶质瘤细胞的调节作用。此外,circYIPF6的下调有效地阻碍了胶质瘤在体内的生长。结论:这些发现提示circYIPF6通过miR-760/PTBP1轴参与胶质瘤的增殖、凋亡和糖酵解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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CircYIPF6 regulates glioma cell proliferation, apoptosis, and glycolysis through targeting miR-760 to modulate PTBP1 expression.

Background: Recent studies have highlighted that circular RNAs regulate cancer-related genes' expression by functioning as microRNA sponges in cancers. Herein, we investigated the function and molecular mechanism of circYIPF6 in glioma.

Methods: 5-Ethynyl-2'-deoxyuridine assay, colony formation, and flow cytometry were performed to assess the proliferation and apoptosis of glioma cells. The levels of glycolytic metabolism were evaluated by measuring the glucose uptake and lactate production. The protein levels of Bax, Bcl2, GLUT1, LDHA, and PTBP1 were examined by western blot. The interplay between miR-760 and circYIPF6 or PTBP1 was confirmed by a dual-luciferase reporter. The effect of circYIPF6 silencing on the growth of glioma in vivo was determined by a xenograft experiment.

Results: circYIPF6 was significantly upregulated in glioma. Knockdown of circYIPF6 suppressed glioma cell proliferation and glycolysis while promoting cell apoptosis. Mechanistic studies revealed that circYIPF6 targeted miR-760 and could abundantly sponge miR-760 to inhibit the expression of its downstream target gene PTBP1. Functional rescue experiments showed that both miR-760 inhibition and PTBP1 overexpression could attenuate the regulatory effect of circYIPF6 silencing on glioma cells. Furthermore, circYIPF6 knocking down effectively impeded glioma growth in vivo.

Conclusion: These findings suggested that circYIPF6 participated in the proliferation, apoptosis, and glycolysis of glioma through the miR-760/PTBP1 axis.

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来源期刊
CiteScore
3.00
自引率
4.80%
发文量
45
审稿时长
>12 weeks
期刊介绍: Translational Neuroscience provides a closer interaction between basic and clinical neuroscientists to expand understanding of brain structure, function and disease, and translate this knowledge into clinical applications and novel therapies of nervous system disorders.
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