Work

TEFM facilitates uterine corpus endometrial carcinoma progression by activating ROS-NFκB pathway

Year: 2024

Type: article

Abstract: BACKGROUND: Mitochondrial transcription elongation factor (TEFM) is a recently discovered factor involved in mitochondrial DNA replication and transcription. Previous studies have reported that abnormal TEFM expression can disrupt the assembly of mitochondrial respiratory chain and thus mitochondrial function. However, the role of TEFM on Uterine corpus endometrial carcinoma (UCEC) progression remains unclear. The present study aims to investigate the expression of TEFM in tumor tissue of UCEC and the effect of abnormal TEFM expression on malignant phenotype of UCEC cells. METHODS: The expressions of TEFM were measured in tumor tissues and cell lines of UCEC by immunohistochemistry, Western blotting, and real-time quantitative PCR assays. Besides, the effects of TEFM knockdown or overexpression on UCEC cell growth, metastasis, apoptosis, and autophagy were also determined using EdU, colony formation, flow cytometry, TUNEL, and transmission electron microscopy assays. Xenograft model was used to confirm the role of TEFM on proliferative potential of UECE cells in vivo. RESULTS: Our bioinformatics analysis of CPTAC data showed that TEFM is abnormally overexpressed in UCEC and its upregulation was significantly associated with poor survival of patients with UCEC. We found that TEFM upregulation significantly promoted the growth and metastasis of UCEC cells. Mechanically, TEFM upregulation impaired the function of mitochondria, decreased their membrane potential and activated the AKT-NFκB pathway by promoting reactive oxygen species (ROS) production, leading to enhanced intracellular autophagy and thus UCEC growth and metastasis. CONCLUSION: This study demonstrates that TEFM positively regulates autophagy to promote the growth and metastasis of UCEC cells, which provides a potential prognostic biomarker and therapeutic target for the treatment of UCEC.

Source: Journal of Translational Medicine

DOI: 10.1186/s12967-024-05833-0