PMAIP1 Enhances DNA Damage and Induces ROS-Mediated Mitochondrial Dysfunction to Suppress Tumorigenesis in Triple-Negative Breast Cancer.

BACKGROUND: PMAIP1 (NOXA) is a pro-apoptotic factor that is closely related to cancer development, but its role in triple-negative breast cancer (TNBC) is unclear. This study aimed to explore the effect of PMAIP1 on TNBC cell viability, apoptosis, DNA damage, and mitochondrial function. METHODS: qRT-PCR and western blot were used to detect the expression level of PMAIP1 in TNBC tissues and cells, and its biological role was evaluated in combination with MTT, TUNEL, comet assay, and mitochondrial function indicators (ROS, ATP, mtDNA, and JC-1). RESULTS: PMAIP1 is significantly upregulated in TNBC and is negatively correlated with cell viability: Overexpression of PMAIP1 inhibits cell viability, while knockdown of PMAIP1 enhances viability. Upregulation of PMAIP1 promotes apoptosis by increasing the Bax/Bcl-2 ratio, induces DNA damage, elevates ROS levels, and reduces ATP, mtDNA, and JC-1 levels, leading to mitochondrial dysfunction; conversely, knockdown of PMAIP1 alleviates these changes. CONCLUSION: PMAIP1 exerts a tumor suppressor effect by regulating apoptosis, DNA damage, and mitochondrial dysfunction, providing potential target support for the treatment of TNBC.