CAMK2B Impacts the Proliferation, Invasion, and Migration of Glioma Cells via the Ras/Raf/MEK/ERK Signaling Pathway.

IF 4.1 4区医学 Q3 ONCOLOGY

Oncology Research Pub Date : 2025-09-26 eCollection Date: 2025-01-01 DOI:10.32604/or.2025.064300

Shiyang Zhang, Jingchen Li, Qianxu Jin, Siyu Zhu, Hongshan Yan, Yizheng Wang, Zihan Song, Liqiang Liu

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引用次数: 0

Abstract

Background: Glioma is the most common tumor of the central nervous system with a poor prognosis. This study aims to explore the role of calcium/calmodulin-dependent protein kinase IIβ (CAMK2B) in regulating the malignant progression of glioma cells, as well as the molecular mechanisms underlying these malignant behaviors.

Methods: The correlation between CAMK2B expression in gliomas and patient prognosis was analyzed using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blot. Furthermore, the study explored the role of CAMK2B in glioma cell proliferation, invasion, and migration using cell counting kit-8 (CCK-8), 5-Ethynyl-2^'-deoxyuridine (EdU), wound healing, transwell, and in vivo tumor xenograft assays.

Result: Patients with high CAMK2B expression exhibited significantly better prognostic outcomes compared to those with low expression levels. Furthermore, CAMK2B expression was significantly lower in glioma tissues and cells compared to both normal brain tissue and human astrocyte cell lines. Notably, overexpression of CAMK2B in glioma cells led to an approximate 40% reduction in proliferative capacity and a 60-70% decrease in invasive and migratory abilities, compared to control glioma cells. These differences were statistically significant at p < 0.05. Conversely, knockdown of CAMK2B using siRNA-CAMK2B significantly enhanced the proliferative, invasive, and migratory capabilities of glioma cells in both in vitro and in vivo settings, enhancing these abilities by 1.5 to 3 times. Notably, these effects were reversed through the application of the Rat Sarcoma viral oncogene homolog (Ras) pathway inhibitor, Salirasib. Western blot analysis revealed that knockdown of CAMK2B led to activation of the Ras/Rapidly Accelerated Fibrosarcoma (Raf)/Mitogen-activated protein kinase kinase (MEK)/Extracellular signal-regulated kinase (ERK) signaling pathway in glioma cell lines, whereas overexpression of CAMK2B resulted in the suppression of this pathway.

Conclusion: CAMK2B inhibits glioma proliferation, invasion, and migration through the Ras/Raf/MEK/ERK signaling pathway.

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CAMK2B通过Ras/Raf/MEK/ERK信号通路影响胶质瘤细胞的增殖、侵袭和迁移

背景：神经胶质瘤是最常见的中枢神经系统肿瘤，预后较差。本研究旨在探讨钙/钙调素依赖性蛋白激酶IIβ (CAMK2B)在调节胶质瘤细胞恶性进展中的作用，以及这些恶性行为的分子机制。方法：采用免疫组织化学、定量逆转录聚合酶链反应（qRT-PCR）和western blot方法分析CAMK2B在胶质瘤组织中的表达与患者预后的关系。此外，该研究通过细胞计数试剂盒-8 （CCK-8）、5-乙基-2'-脱氧尿苷（EdU）、伤口愈合、transwell和体内肿瘤异种移植试验探讨了CAMK2B在胶质瘤细胞增殖、侵袭和迁移中的作用。结果：CAMK2B高表达患者的预后明显好于低表达患者。此外，CAMK2B在胶质瘤组织和细胞中的表达明显低于正常脑组织和人类星形胶质细胞细胞系。值得注意的是，与对照胶质瘤细胞相比，CAMK2B在胶质瘤细胞中的过表达导致增殖能力降低约40%，侵袭和迁移能力降低60-70%。差异有统计学意义，p < 0.05。相反，使用siRNA-CAMK2B敲除CAMK2B可显著增强胶质瘤细胞在体内和体外的增殖、侵袭和迁移能力，将这些能力提高1.5 - 3倍。值得注意的是，通过应用大鼠肉瘤病毒癌基因同源物（Ras）途径抑制剂Salirasib，这些作用被逆转。Western blot分析显示，CAMK2B的敲低导致胶质瘤细胞系Ras/ fast - Accelerated Fibrosarcoma (Raf)/Mitogen-activated protein kinase kinase (MEK)/Extracellular signal-regulated kinase （ERK）信号通路的激活，而CAMK2B的过表达导致该通路的抑制。结论：CAMK2B通过Ras/Raf/MEK/ERK信号通路抑制胶质瘤的增殖、侵袭和迁移。

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

Oncology Research 医学-肿瘤学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.