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

Fangjian Shang1,2, Lei Xu3, Hongzhi Liu2

  • 1Department of General Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, 050023, Hebei, China, hebmu.edu.cn.

The Breast Journal
|January 1, 2026
PubMed
Abstract

Insights

PMAIP1 (NOXA) suppresses triple-negative breast cancer (TNBC) by promoting apoptosis and DNA damage while impairing mitochondrial function. Upregulation of PMAIP1 inhibits TNBC cell viability, indicating its potential as a therapeutic target.

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.
Keywords:
DNA damagePMAIP1 (NOXA)apoptosismitochondrial dysfunctiontriple-negative breast cancer (TNBC)

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