Abstract

Background

Glioblastoma stem cells (GSCs) are a subpopulation of glioblastoma (GBM) cells that are critical for tumor invasion and treatment resistance. However, little is known about the function and mechanism of tripartite motif-containing 24 (TRIM24) in GSCs.

Methods

Immunofluorescence, flow cytometry, and western blot analyses were used to evaluate TRIM24 and cluster of differentiation (CD)133 expression profiles in GBM surgical specimens and GSC tumorspheres. Different TRIM24 expression levels in patients’ tumors, as measured by both immunohistochemistry and western blot, were related to their corresponding MRI data. Wound healing, Matrigel invasion, and xenograft immunohistochemistry were conducted to determine GBM cell invasion.

Results

We identified that TRIM24 was coexpressed with CD133 and Nestin in GBM tissues and tumorsphere cells. Limiting dilution assays and xenotransplantation experiments illustrated that knockdown of TRIM24 expression reduced GSC self-renewal capacity and invasive growth. TRIM24 expression levels were positively associated with the volumes of peritumoral T2 weighted image abnormality. Rescue experiments indicated TRIM24 participation in GBM infiltrative dissemination. Chromatin immunoprecipitation, reporter gene assay, PCR, western blot, and immunohistochemistry demonstrated that TRIM24 activated the expression of the pluripotency transcription factor sex determining region Y–box 2 (Sox2) to regulate GBM stemness and invasion in vitro and in vivo. Finally, the close relationship between TRIM24 and Sox2 was validated by testing samples enrolled in our study and exploring external databases.

Conclusions

Our findings uncover essential roles of the TRIM24–Sox2 axis in GBM stemness and invasiveness, suggesting TRIM24 as a potential target for effective GBM management.

中文翻译：

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TRIM24 通过激活 SOX2 表达促进胶质母细胞瘤细胞的干性和侵袭性。

摘要

背景

胶质母细胞瘤干细胞 (GSC) 是胶质母细胞瘤 (GBM) 细胞的一个亚群，对肿瘤侵袭和治疗抗性至关重要。然而，关于含三联基序的 24 (TRIM24) 在 GSCs 中的功能和机制知之甚少。

方法

免疫荧光、流式细胞术和蛋白质印迹分析用于评估 GBM 手术标本和 GSC 肿瘤球中的 TRIM24 和分化簇 (CD)133 表达谱。通过免疫组织化学和蛋白质印迹测量，患者肿瘤中不同的 TRIM24 表达水平与其相应的 MRI 数据相关。进行伤口愈合、基质胶侵袭和异种移植免疫组织化学以确定 GBM 细胞侵袭。

结果

我们发现TRIM24 在GBM 组织和肿瘤球细胞中与CD133 和Nestin 共表达。有限稀释测定和异种移植实验表明，TRIM24 表达的敲低降低了 GSC 自我更新能力和侵入性生长。TRIM24 表达水平与肿瘤周围 T2 加权图像异常的体积呈正相关。救援实验表明 TRIM24 参与了 GBM 的渗透传播。染色质免疫沉淀、报告基因检测、PCR、蛋白质印迹和免疫组织化学表明，TRIM24 激活多能性转录因子性别决定区 Y-box 2 (Sox2) 的表达，从而在体外和体内调节 GBM 干性和侵袭。最后，

结论

我们的研究结果揭示了 TRIM24-Sox2 轴在 GBM 干性和侵袭性中的重要作用，表明 TRIM24 作为有效 GBM 管理的潜在目标。