Open Access

ARTICLE

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

Shiyang Zhang^1,#, Jingchen Li^1,#, Qianxu Jin², Siyu Zhu¹, Hongshan Yan², Yizheng Wang³, Zihan Song¹, Liqiang Liu^1,*

1 Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China
2 Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, China
3 Department of Pain and Rehabilitation, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, China

* Corresponding Author: Liqiang Liu. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research 2025, 33(10), 2961-2979. https://doi.org/10.32604/or.2025.064300

Received 11 February 2025; Accepted 01 August 2025; Issue published 26 September 2025

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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