The role and prognostic value of mitochondria-related gene PARK7 in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor among women globally, with incidence and mortality rates ranking first among female cancers. Mitochondrial dysfunction plays a crucial role in the occurrence, development, and metastasis of breast cancer, but the specific mechanisms remain unclear. This study aims to explore the mechanisms and prognostic value of the mitochondrial-related gene PARK7 in breast cancer. METHODS: This study integrated summary data on the methylation levels, expression levels, and protein abundance of mitochondrial-related genes. The discovery phase data were sourced from the IEU GWAS database, while the validation phase data came from the FinnGen study dataset. Mendelian randomization and colocalization analyses were conducted to explore the potential associations between the methylation, expression, and protein abundance of mitochondrial-related genes and breast cancer risk. Clinical and pathological data, as well as gene expression data from breast cancer patients, were obtained from the TCGA database. Cox regression analysis was used to assess the relationship between PARK7 expression and clinical pathological features, and a prognostic model was constructed. Additionally, in vitro experiments were performed to verify the effects of PARK7 on triple-negative breast cancer cells. RESULTS: The study found that high expression of the PARK7 gene is closely related to a reduced risk of breast cancer (OR 0.91, 95% Cl 0.88-0.95; PPH4 = 0.90), which was also validated in the FinnGen dataset. Patients with high PARK7 expression had longer survival times and higher survival probabilities in the TCGA database. In vitro experiments showed that overexpression of PARK7 significantly inhibited the proliferation, migration, and colony formation of triple-negative breast cancer cells, while promoting apoptosis and significantly increasing mitochondrial membrane potential, indicating altered mitochondrial function. Furthermore, Western blot analysis revealed that overexpression of PARK7 led to increased PTEN protein expression and decreased p-PI3K and p-AKT protein expression, suggesting that PARK7 may exert its tumor-suppressive effects by modulating the PI3K/Akt signaling pathway. CONCLUSION: High expression of the PARK7 gene is closely related to reduced breast cancer risk and good prognosis, and it may exert its tumor-suppressive effects by regulating the expression of apoptosis-related proteins and migration-related proteins, as well as by affecting mitochondrial function and modulating the PI3K/Akt signaling pathway. It can serve as a potential biomarker for the diagnosis, treatment, and prognosis of breast cancer.