8.A.239.  The Cox19 Assembly Protein (Cox19) Family

Copper (Cu) plays an important role in the progression of tumor diseases. Metastasis associated with colon cancer protein 1 (MACC1) promotes the transcription and expression of various tumor-related genes. Cytochrome c oxidase (COX) 19, present in the cytoplasm and intermembrane space of mitochondria, may transport Cu within the mitochondria. The mechanism through which MACC1 initiates the transcription and expression of COX19, and promotes malignant behavior in tumor cells is of interest (Gao et al. 2024). The expression of the MACC1 and COX19 genes in tumors and normal tissues has been measured. RNA-chromatin immunoprecipitation was used to detect the transcriptional initiation of COX19 by MACC1. The effects of MACC1 and COX19 on mitochondrial activity were determined using an ATP assay kit and Cytochrome c Oxidase Assay Kit. A Cell Counting Kit-8 kit was used to detect the effect of high-dose Cu or overexpression of MACC1 and COX19 on tumor cell proliferation. 

Cu enhanced the proliferation, invasion, and migration and inhibited apoptosis of SW480 cells. MACC1 was highly expressed in colorectal cancer tissues and activated the expression of COX19 by binding to the promoter region of COX19. The overexpression of COX19 increased mitochondrial Cu content and enhanced the activity of mitochondrial COX and ATP content, but inhibited apoptosis, promoted tumor growth of mice. This indicated that COX19 functions as a target gene of MACC1 and regulates mitochondrial activity while promoting the progression of colorectal cancer. MACC1/COX19 may provide a novel therapeutic target for colorectal cancer (Gao et al. 2024).