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.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Humans , AMP-Activated Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , TOR Serine-Threonine Kinases/metabolism , Cell Proliferation/genetics , DNA, Mitochondrial/genetics , Mitochondria/metabolism , HCT116 Cells , Cell Line, Tumor , Colonic Neoplasms/metabolism , Adenosine Triphosphate/metabolism , Colorectal Neoplasms/pathology , Gene Expression Regulation, NeoplasticABSTRACT
Breast cancer (BC) and colon cancer (CRC) are the two most deadly cancers in the world. These cancers partly share the same genetic background and are partially regulated by the same genes. The outcomes of traditional chemoradiotherapy and surgery remain suboptimal, with high postoperative recurrence and a low survival rate. It is, therefore, urgent to innovate and improve the existing treatment measures. Many studies primarily reported that the microRNA (miRNA) sponge functions of circular RNA (circRNA) in BC and CRC have an indirect relationship between the circRNA-miRNA axis and malignant behaviors. With a covalent ring structure, circRNAs can regulate the expression of target genes in multiple ways, especially by acting as miRNA sponges. Therefore, this review mainly focuses on the roles of circRNAs as miRNA sponges in BC and CRC based on studies over the last three years, thus providing a theoretical reference for finding new therapeutic targets in the future.