2. Academic Validation
  3. TEFM facilitates uterine corpus endometrial carcinoma progression by activating ROS-NFκB pathway

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

  • J Transl Med. 2024 Dec 27;22(1):1151. doi: 10.1186/s12967-024-05833-0.
Jia Lei # 1 2 3,  Qingguo Zhu # 4,  Jianghao Guo # 4,  Jiaxing Chen 4,  Lixia Qi 4,  Mengmeng Cui 4,  Zhixiong Jiang 4,  Chunhui Fan 4,  Lin Wang 2,  Tianjiao Lai 1 3,  Yuxi Jin 1 3,  Lulu Si 1 3,  Yana Liu 1 3,  Qi Yang 5 6,  Dengke Bao 7 8,  Ruixia Guo 9 10
Affiliations

Affiliations

  • 1 Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 2 Radiotheraphy Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
  • 3 Henan Key Medical Laboratory for the Prevention and Treatment of Gynecological Malignant Tumors, Zhengzhou, Henan, 450052, China.
  • 4 Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China.
  • 5 Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China. yangqi_456@126.com.
  • 6 School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China. yangqi_456@126.com.
  • 7 Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China. bdkmydy12004@126.com.
  • 8 The First Affiliated Hospital of Henan University, Henan University, Kaifeng, Henan, 475004, China. bdkmydy12004@126.com.
  • 9 Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. grxcdxzzu@163.com.
  • 10 Henan Key Medical Laboratory for the Prevention and Treatment of Gynecological Malignant Tumors, Zhengzhou, Henan, 450052, China. grxcdxzzu@163.com.
  • # Contributed equally.
PMID: 39731053 DOI: 10.1186/s12967-024-05833-0
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.

Keywords

Mitochondria; NFκB pathway; ROS; TEFM; Uterine corpus endometrial carcinoma.

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