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PHF5A Epigenetically Inhibits Apoptosis to Promote Breast Cancer Progression

Yi-Zi Zheng1,2, Meng-Zhu Xue3, Hong-Jie Shen4

  • 1Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.

Cancer Research
|April 28, 2018
PubMed

Insights

PHD finger protein 5A (PHF5A) promotes breast cancer by suppressing apoptosis. Targeting PHF5A may offer a new therapeutic strategy for aggressive breast cancers, including triple-negative subtypes.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Alternative splicing (AS) dysregulation is crucial in cancer, but its role in breast cancer remains unclear.
  • RNA-binding proteins are key regulators of AS, influencing tumor development.
  • Identifying specific splicing factors involved in breast cancer progression is essential.

Purpose of the Study:

  • To investigate the role of RNA-binding proteins in breast cancer development.
  • To identify key splicing factors contributing to breast cancer progression.
  • To elucidate the molecular mechanisms underlying PHF5A's function in breast cancer.

Main Methods:

  • Conducted an in vivo CRISPR screen targeting RNA-binding proteins.
  • Assessed PHF5A expression in breast cancer specimens.
  • Performed knockdown experiments to evaluate PHF5A's functional impact.
  • Investigated the interaction of PHF5A with the SF3b spliceosome and histones.
  • Analyzed the PHF5A-FASTK axis in breast cancer samples.

Main Results:

  • PHD finger protein 5A (PHF5A) was identified as a critical splicing factor in breast cancer.
  • PHF5A is upregulated in breast cancer, correlating with poor survival.
  • PHF5A knockdown suppressed tumor cell proliferation, migration, and formation.
  • PHF5A stabilizes the SF3b spliceosome and influences alternative splicing of apoptotic genes.
  • PHF5A ablation increased truncated FASTK, enhancing Fas-mediated apoptosis.

Conclusions:

  • PHF5A acts as an epigenetic suppressor of apoptosis, driving breast cancer progression.
  • The PHF5A-modulated FASTK-AS axis is prevalent in breast cancer, especially triple-negative subtypes.
  • PHF5A represents a potential therapeutic target for breast cancer treatment.

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