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

Area of Science:

• Molecular Biology
• Cancer Research
• Cell Biology

Background:

• PMAIP1 (NOXA) is a pro-apoptotic factor implicated in cancer, but its specific role in triple-negative breast cancer (TNBC) remains largely unknown.
• Understanding PMAIP1's function in TNBC is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the effect of PMAIP1 on TNBC cell viability, apoptosis, DNA damage, and mitochondrial function.
• To elucidate the potential of PMAIP1 as a therapeutic target for TNBC.

Main Methods:

• Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were employed to assess PMAIP1 expression in TNBC tissues and cells.
• Cell viability was evaluated using MTT assays, apoptosis was detected by TUNEL assays, and DNA damage was assessed via comet assays.
• Mitochondrial function was analyzed by measuring reactive oxygen species (ROS), ATP levels, mitochondrial DNA (mtDNA) content, and JC-1 staining.

Main Results:

• PMAIP1 expression was significantly upregulated in TNBC and inversely correlated with cell viability; PMAIP1 overexpression inhibited viability, whereas its knockdown enhanced it.
• Overexpression of PMAIP1 promoted apoptosis by increasing the Bax/Bcl-2 ratio, induced DNA damage, elevated ROS levels, and decreased ATP, mtDNA, and JC-1 levels, indicating mitochondrial dysfunction.
• Conversely, knockdown of PMAIP1 reversed these effects, alleviating apoptosis, DNA damage, and mitochondrial dysfunction.

Conclusions:

• PMAIP1 exhibits tumor suppressor activity in TNBC by modulating apoptosis, DNA damage, and mitochondrial dysfunction.
• These findings highlight PMAIP1 as a promising therapeutic target for TNBC treatment.