Wang Yin, Hu Wenxuan, Zhou Boya, Zhao Yu, Tang Yufei, Deng Zhiyong, Chen Minbin
Institute for Excellence in Clinical Medicine of Kunshan First People's Hospital, Soochow University, Suzhou, China.
Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Cancer Cell Int. 2024 Dec 24;24(1):429. doi: 10.1186/s12935-024-03617-6.
Gliomas are the most common tumors of the central nervous system, with glioblastoma (GBM) being particularly aggressive and fatal. Current treatments for GBM, including surgery and chemotherapy, are limited by tumor aggressiveness and the blood-brain barrier. Therefore, understanding the molecular mechanisms driving GBM growth is essential. Mitochondria, key players in cellular energy production, have been implicated in cancer development. In this study, we investigated the expression of mitochondrial transcription elongation factor (TEFM) in gliomas and its potential role in tumor progression. Analysis of data from The Cancer Genome Atlas (TCGA) revealed that TEFM transcript levels were significantly higher in glioma tissues compared to adjacent normal tissues. High TEFM expression was associated with poor survival outcomes in glioma patients. Furthermore, TEFM was notably upregulated in glioma tissue and in primary glioma cells derived from local patients, while its expression was relatively low in normal tissues and astrocytes. Silencing or knockout of TEFM significantly inhibited glioma cell growth, proliferation, clonogenicity, migration, and invasion, while inducing apoptosis and activating caspases. In contrast, ectopic overexpression of TEFM promoted tumorigenic activity, enhancing the malignant behavior of glioma cells. Co-expression analysis identified a strong correlation between TEFM and the epithelial-mesenchymal transition (EMT) pathway in gliomas. Notably, the expression of EMT markers, such as N-cadherin and Vimentin, decreased upon TEFM knockdown or knockout. Additionally, TEFM depletion impaired mitochondrial function, disrupting the mitochondrial respiratory chain in glioma cells. In vivo experiments demonstrated that TEFM knockout effectively suppressed the growth of subcutaneous glioma xenografts in nude mice. Collectively, these findings highlight the critical role of TEFM in GBM growth and invasion, suggesting that it could serve as a promising therapeutic target for glioma treatment.
神经胶质瘤是中枢神经系统最常见的肿瘤，其中胶质母细胞瘤（GBM）尤其具有侵袭性且致命。目前针对GBM的治疗方法，包括手术和化疗，受到肿瘤侵袭性和血脑屏障的限制。因此，了解驱动GBM生长的分子机制至关重要。线粒体是细胞能量产生的关键参与者，与癌症发展有关。在本研究中，我们调查了线粒体转录延伸因子（TEFM）在神经胶质瘤中的表达及其在肿瘤进展中的潜在作用。对癌症基因组图谱（TCGA）数据的分析显示，与相邻正常组织相比，神经胶质瘤组织中TEFM转录水平显著更高。TEFM高表达与神经胶质瘤患者的不良生存结果相关。此外，TEFM在神经胶质瘤组织和源自当地患者的原发性神经胶质瘤细胞中显著上调，而其在正常组织和星形胶质细胞中的表达相对较低。沉默或敲除TEFM显著抑制神经胶质瘤细胞的生长、增殖、克隆形成、迁移和侵袭，同时诱导细胞凋亡并激活半胱天冬酶。相反，TEFM的异位过表达促进了致瘤活性，增强了神经胶质瘤细胞的恶性行为。共表达分析确定了TEFM与神经胶质瘤中的上皮-间质转化（EMT）途径之间存在强相关性。值得注意的是，在TEFM敲低或敲除后，EMT标志物如N-钙黏蛋白和波形蛋白的表达降低。此外，TEFM缺失损害了线粒体功能，破坏了神经胶质瘤细胞中的线粒体呼吸链。体内实验表明，TEFM敲除有效地抑制了裸鼠皮下神经胶质瘤异种移植瘤的生长。总的来说，这些发现突出了TEFM在GBM生长和侵袭中的关键作用，表明它可能成为神经胶质瘤治疗的一个有前景的治疗靶点。
