2. Academic Validation
  3. Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells

Modulating p-AMPK/mTOR Pathway of Mitochondrial Dysfunction Caused by MTERF1 Abnormal Expression in Colorectal Cancer Cells

  • Int J Mol Sci. 2022 Oct 15;23(20):12354. doi: 10.3390/ijms232012354.
Qianqian Liu 1 2,  Longlong Zhang 1 2,  Yayan Zou 1,  Ying Tao 1,  Bing Wang 1,  Bin Li 3 4,  Ruai Liu 3 4,  Boyong Wang 3 4,  Lei Ding 1,  Qinghua Cui 1,  Jie Lin 1,  Bingyu Mao 5,  Wei Xiong 3 4,  Min Yu 1
Affiliations

Affiliations

  • 1 School of Life Sciences, Yunnan University, Kunming 650091, China.
  • 2 State Key Laboratory for Conservation and Utilization of Bio-Resources, Key Laboratory for Microbial Resources of the Ministry of Education, School of Life Sciences, Yunnan University, Kunming 650091, China.
  • 3 College of Basic Medical Sciences, Dali University, Dali 671000, China.
  • 4 Yunnan Key Laboratory of Screening and Research on Anti-Pathogenic Plant Resources from Western Yunnan, Dali University, Dali 671000, China.
  • 5 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
PMID: 36293209 DOI: 10.3390/ijms232012354
Abstract

Human mitochondrial transcription termination factor 1 (MTERF1) has been demonstrated to play an important role in mitochondrial gene expression regulation. However, the molecular mechanism of MTERF1 in colorectal Cancer (CRC) remains largely unknown. Here, we found that MTERF1 expression was significantly increased in colon Cancer tissues compared with normal colorectal tissue by Western blotting, immunohistochemistry, and tissue microarrays (TMA). Overexpression of MTERF1 in the HT29 cell promoted cell proliferation, migration, invasion, and xenograft tumor formation, whereas knockdown of MTERF1 in HCT116 cells appeared to be the opposite phenotype to HT29 cells. Furthermore, MTERF1 can increase mitochondrial DNA (mtDNA) replication, transcription, and protein synthesis in colorectal Cancer cells; increase ATP levels, the mitochondrial crista density, mitochondrial membrane potential, and oxygen consumption rate (OCR); and reduce the ROS production in colorectal Cancer cells, thereby enhancing mitochondrial Oxidative Phosphorylation (OXPHOS) activity. Mechanistically, we revealed that MTERF1 regulates the AMPK/mTOR signaling pathway in cancerous cell lines, and we also confirmed the involvement of the AMPK/mTOR signaling pathway in both xenograft tumor tissues and colorectal Cancer tissues. In summary, our data reveal an oncogenic role of MTERF1 in CRC progression, indicating that MTERF1 may represent a new therapeutic target in the future.

Keywords

AMPK/mTOR; MTERF1; cell proliferation; colorectal cancer; mtDNA; oxidative phosphorylation.

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