Department of Neurosurgery, the First Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of Neurosurgery, the Second Hospital of PLA Southern Navy, Sanya, Hainan, China.
Neuro Oncol. 2020 Dec 18;22(12):1797-1808. doi: 10.1093/neuonc/noaa138.
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.
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.
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.
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.
神经胶质瘤干细胞（GSCs）是神经胶质瘤（GBM）细胞的一个亚群，对肿瘤侵袭和治疗耐药至关重要。然而，TRIM24 在 GSCs 中的功能和机制知之甚少。
免疫荧光、流式细胞术和 Western blot 分析用于评估 GBM 手术标本和 GSC 肿瘤球体中 TRIM24 和分化簇（CD）133 的表达谱。通过免疫组化和 Western blot 测量患者肿瘤中不同的 TRIM24 表达水平与相应的 MRI 数据相关。通过划痕愈合、Matrigel 侵袭和异种移植免疫组化来确定 GBM 细胞侵袭。
我们发现 TRIM24 与 CD133 和 Nestin 在 GBM 组织和肿瘤球体细胞中共同表达。有限稀释测定和异种移植实验表明，敲低 TRIM24 表达降低了 GSC 的自我更新能力和侵袭性生长。TRIM24 表达水平与肿瘤周围 T2 加权图像异常的体积呈正相关。挽救实验表明 TRIM24 参与了 GBM 的浸润性扩散。染色质免疫沉淀、报告基因测定、PCR、Western blot 和免疫组化表明，TRIM24 激活多能性转录因子性别决定区 Y 框 2（Sox2）的表达，调节体外和体内 GBM 干性和侵袭性。最后，通过测试我们研究中纳入的样本并探索外部数据库，验证了 TRIM24 和 Sox2 之间的密切关系。
我们的发现揭示了 TRIM24-Sox2 轴在 GBM 干性和侵袭性中的重要作用，表明 TRIM24 可能是有效管理 GBM 的潜在靶点。
