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Proteomic Characterization of AS1411 Reveals ATP6AP1 as a Mediator of Triple-Negative Breast Cancer Progression

Ha-Song Bae1, Yun-Jeong Seo1, Eun-Bi Kim1

  • 1Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, Republic of Korea.

Proteomics
|March 27, 2026
PubMed

Insights

The DNA aptamer AS1411 effectively targets nucleolin (NCL) to reduce triple-negative breast cancer (TNBC) cell growth and migration. This study identifies ATPase H+-transporting accessory protein 1 (ATP6AP1) as a key mediator, suggesting it as a potential therapeutic target for TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and limited treatment options.
  • Nucleolin (NCL) is a potential therapeutic target in various cancers, including TNBC.

Purpose of the Study:

  • To elucidate the molecular mechanisms behind the anticancer effects of the NCL-targeting DNA aptamer AS1411 in TNBC.
  • To identify novel therapeutic targets for TNBC treatment.

Main Methods:

  • Label-free quantitative proteomic profiling of AS1411-treated TNBC cells.
  • Bioinformatic analysis of differentially expressed proteins (DEPs) and associated signaling pathways.
  • Functional studies involving knockdown and overexpression of identified key proteins.

Main Results:

  • AS1411 treatment significantly inhibited TNBC cell viability and migration.
  • Proteomic analysis revealed downregulation of ATPase H+-transporting accessory protein 1 (ATP6AP1) in response to AS1411.
  • ATP6AP1 knockdown suppressed TNBC proliferation and migration, while its overexpression promoted tumorigenic phenotypes, with minimal impact on normal cells.

Conclusions:

  • ATP6AP1 is identified as a critical downstream mediator of AS1411's anticancer effects in TNBC.
  • ATP6AP1 represents a promising therapeutic target for the treatment of triple-negative breast cancer.
Keywords:
AS1411ATP6AP1proteomicstriple‐negative breast cancer

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