mtDNA copy number/ axis in invasive ductal carcinoma of the breast.

INTRODUCTION

Mitochondrial DNA (mtDNA) copy number variations have been reported in multiple human cancers. Previous studies indicate that mitochondrial retrograde signaling regulates , which plays a key role in tumorigenesis, including regulating apoptosis antagonizing transcription factor (). This study investigates the expression of and in relation to mtDNA copy number in invasive ductal carcinoma (IDC) of the breast.

METHODS

Paired primary tumors and adjacent non-tumor tissues were analyzed to assess changes in and expression using fold-change analysis. The mtDNA copy number was quantified using as the mitochondrial gene and as the nuclear control gene. To validate the findings, publicly available data from The Cancer Genome Atlas (TCGA) were also analyzed.

RESULTS

A significant reduction in tumor expression was observed (fold change=0.139), with a strong correlation between and expression. A significant Z-score difference was also detected between and mtDNA copy number. was predominantly expressed in grade I tumors but significantly downregulated in higher-grade tumors, whereas expression increased with tumor grade. In silico analysis of TCGA data confirmed elevated expression, with notable variations across breast cancer subtypes.

CONCLUSION

We observed reduced expression of and mtDNA copy number in breast tumors, along with variations in levels across subtypes. The decrease in could be associated with lower mtDNA copy numbers and impaired retrograde signaling, impacting expression and function. Our findings underscore the therapeutic promise of targeting the mtDNA/miR-663/AATF axis, which could lead to advancements in breast cancer treatment.