Mitochondrial transcription elongation factor TEFM promotes malignant progression of gliomas

Yin Wang; Wenxuan Hu; Boya Zhou; Yu Zhao; Yufei Tang; Zhiyong Deng; Minbin Chen

doi:10.1186/s12935-024-03617-6

Mitochondrial transcription elongation factor TEFM promotes malignant progression of gliomas

Cancer Cell Int. 2024 Dec 24;24(1):429. doi: 10.1186/s12935-024-03617-6.

Authors

Yin Wang^#¹, Wenxuan Hu^#², Boya Zhou^#³, Yu Zhao⁴, Yufei Tang⁴, Zhiyong Deng⁵, Minbin Chen^{6

7}

Affiliations

¹ Institute for Excellence in Clinical Medicine of Kunshan First People's Hospital, Soochow University, Suzhou, China.
² Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
³ Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
⁴ Department of Soochow Medical College, Soochow University, Suzhou, China.
⁵ Institute for Excellence in Clinical Medicine of Kunshan First People's Hospital, Soochow University, Suzhou, China. yichun1988@yeah.net.
⁶ Institute for Excellence in Clinical Medicine of Kunshan First People's Hospital, Soochow University, Suzhou, China. mbinchen@163.com.
⁷ Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China. mbinchen@163.com.

^# Contributed equally.

PMID: 39719635
DOI: 10.1186/s12935-024-03617-6

Abstract

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.

Keywords: EMT; Gliomas; Mitochondria; TEFM.