Introduction

Glioblastoma multiforme (GBM) poses a significant challenge in terms of treatment due to its high malignancy, necessitating the identification of additional molecular targets. VSIG4, an oncogenic gene participates in tumor growth and migration in various cancer types. Nevertheless, the precise process through which VSIG4 facilitates the malignant progression of glioma remains to be elucidated.

Objectives

This research aims to explore the function and molecular mechanism involving VSIG4 in the malignant progression of glioma.

Methods

The amount of VSIG4 was measured using qPCR, western blotting, and immunohistochemistry. Lentivirus infections were applied for upregulating or downregulating molecules within glioma cells. The incorporation of 5-ethynyl-20-deoxyuridine, Transwell, cell counting kit-8, and clone formation experiments, were applied to assess the biological functions of molecules on glioma cells. Dual luciferase reporter gene, RNA immunoprecipitation, and chromatin immunoprecipitation assays were used to explore the functional relationship among relevant molecules.

Results

The upregulation of VSIG4 was observed in GBM tissues, indicating an adverse prognosis. Silencing VSIG4 in glioma cells resulted in a decrease in cell viability, invasion, proliferation, and tumorigenesis, an increase in cell apoptosis, and a stagnation in the cell cycle progression at the G0/G1 phase. Mechanistically, SPI1-mediated upregulation of VSIG4 expression led to binding between VSIG4 and THBS1 protein, ultimately facilitating the malignant progression of glioma cells through the activation of the PI3K/AKT pathway. The inhibited proliferative and invasive capabilities of glioma cells were reversed by overexpressing THBS1 following the knockdown of VSIG4.

Conclusion

Our findings provide evidence for the role of VSIG4 as an oncogene and reveal the previously unidentified contribution of the SPI1/VSIG4/THBS1 axis in the malignant progression of glioma. This signaling cascade enhances tumor growth and invasion by modulating the PI3K/AKT pathway. VSIG4 as a potential biomarker may be a viable strategy in the development of tailored molecular therapies for GBM.

中文翻译：

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SPI1/VSIG4/THBS1 通过调节 PI3K/AKT 通路对胶质母细胞瘤进展的作用

 介绍

多形性胶质母细胞瘤 （GBM） 由于其高度恶性，在治疗方面构成了重大挑战，需要确定额外的分子靶点。VSIG4 是一种致癌基因，参与各种癌症类型的肿瘤生长和迁移。然而，VSIG4 促进神经胶质瘤恶性进展的确切过程仍有待阐明。

 目标

本研究旨在探讨 VSIG4 在胶质瘤恶性进展中的功能和分子机制。

 方法

使用 qPCR 、 western blotting 和免疫组织化学测量 VSIG4 的量。慢病毒感染用于上调或下调神经胶质瘤细胞内的分子。掺入 5-乙炔基-20-脱氧尿嘧啶、Transwell、细胞计数试剂盒-8 和克隆形成实验，以评估分子在神经胶质瘤细胞上的生物学功能。采用双荧光素酶报告基因、 RNA 免疫沉淀和染色质免疫沉淀法探讨相关分子之间的功能关系。

 结果

在 GBM 组织中观察到 VSIG4 的上调，表明预后不良。沉默神经胶质瘤细胞中的 VSIG4 导致细胞活力、侵袭、增殖和肿瘤发生降低，细胞凋亡增加，以及 G0/G1 期细胞周期进程停滞。从机制上讲，SPI1 介导的 VSIG4 表达上调导致 VSIG4 和 THBS1 蛋白之间的结合，最终通过激活 PI3K/AKT 通路促进胶质瘤细胞的恶性进展。敲低 VSIG4 后过表达 THBS1 可逆转神经胶质瘤细胞的抑制增殖和侵袭能力。

 结论

我们的研究结果为 VSIG4 作为癌基因的作用提供了证据，并揭示了 SPI1/VSIG4/THBS1 轴在神经胶质瘤恶性进展中先前未被确定的贡献。这种信号级联反应通过调节 PI3K/AKT 通路来增强肿瘤生长和侵袭。VSIG4 作为一种潜在的生物标志物可能是开发针对 GBM 的定制分子疗法的可行策略。