CircBUB1 activates the PI3K/AKT signaling pathway to promote the migration and invasion of glioblastoma cells

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuropeptides Pub Date : 2023-12-13 DOI:10.1016/j.npep.2023.102400

Runan Zhang, Dongmei Wu, Ying Wang, Liping Wu, Guowei Gao, Dayong Shan

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Abstract

Background

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid growth and resistance to treatment, leading to poor survival rates. The molecular mechanisms underlying GBM progression remain unclear, necessitating further research. This study focuses on the role of circBUB1, a circular RNA, in GBM cell migration and invasion, and the associated molecular mechanisms.

Methods

RNA/protein expression was detected using RT-qPCR/western blot assay. Transwell and wound healing assays were conducted to assess GBM cell migration and invasion. Detailed mechanistic analyses were carried out to understand the role of circBUB1 in GBM cells.

Results

CircBUB1 was found to be highly expressed and functioned as an oncogene in GBM cells. Functional assays revealed that knockdown of circBUB1 suppressed the migration and invasion of GBM cells. Mechanistic analyses showed that circBUB1 sequestered miR-1296-5p, thereby elevating TRIM14 expression. TRIM14 was also found to promote PTEN ubiquitination, ultimately leading to the down-regulation of PTEN protein and activation of the PI3K/AKT signaling pathway. Through rescue assays, this study confirmed that circBUB1 promoted GBM cell migration and invasion by reducing PTEN protein levels.

Conclusion

Our findings indicate that circBUB1 activates the PI3K/AKT signaling pathway, promoting the migration and invasion of GBM cells via the miR-1296-5p/TRIM14 axis. This provides new insights into the molecular mechanisms of GBM progression and potential therapeutic targets.

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CircBUB1 激活 PI3K/AKT 信号通路，促进胶质母细胞瘤细胞的迁移和侵袭

背景胶质母细胞瘤（GBM）是侵袭性最强的原发性脑肿瘤，其特点是生长迅速、耐药，导致生存率低下。GBM进展的分子机制仍不清楚，需要进一步研究。本研究主要探讨环状 RNA circBUB1 在 GBM 细胞迁移和侵袭中的作用及其相关分子机制。采用 Transwell 和伤口愈合试验评估 GBM 细胞的迁移和侵袭。为了解 circBUB1 在 GBM 细胞中的作用，进行了详细的机理分析。功能测试显示，敲除 circBUB1 可抑制 GBM 细胞的迁移和侵袭。机理分析表明，circBUB1能封闭miR-1296-5p，从而提高TRIM14的表达。研究还发现，TRIM14能促进PTEN泛素化，最终导致PTEN蛋白下调并激活PI3K/AKT信号通路。结论我们的研究结果表明，circBUB1 激活了 PI3K/AKT 信号通路，通过 miR-1296-5p/TRIM14 轴促进了 GBM 细胞的迁移和侵袭。这为研究 GBM 进展的分子机制和潜在治疗靶点提供了新的视角。

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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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.