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ALYREF enhances breast cancer progression by regulating EZH2.

Su-Jin Jeong1,2, Ji Hoon Oh1,2, Je-Yoel Cho1,2

  • 1Department of Biochemistry, College of Veterinary Medicine, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, Republic of Korea.

Heliyon
|October 10, 2024
PubMed
Summary

Canine mammary tumors (CMTs) and human breast cancer share similarities. Researchers found elevated ALYREF gene expression in CMTs and human breast cancer, linking it to poor prognosis and malignant transformation via epigenetic regulation.

Keywords:
ALYREFBreast cancerCanine mammary tumorEpigenetics

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Area of Science:

  • Comparative oncology
  • Epigenetics
  • Molecular biology

Background:

  • Canine mammary tumors (CMTs) are common in female dogs and serve as models for human breast cancer.
  • Histone modifications in CMTs remain understudied compared to human breast cancer.

Purpose of the Study:

  • To compare the Histone H3 lysine 4 trimethylation (H3K4me3) landscape in canine mammary tumors with human breast cancer.
  • To investigate the role of the ALYREF gene in canine and human mammary tumors.

Main Methods:

  • Histone H3 lysine 4 trimethylation (H3K4me3) ChIP-seq analysis in canine mammary tumors.
  • RNA-sequencing data analysis (publicly available and from the study).
  • ALYREF gene expression and functional assays (depletion studies).

Main Results:

  • Significant enrichment of H3K4me3 in the ALYREF gene promoter of canine mammary tumor tissues.
  • Elevated ALYREF expression in malignant tissues and cell lines, associated with poor prognosis in humans.
  • ALYREF depletion altered cellular phenotypes, decreasing apoptosis and increasing proliferation and colony formation.

Conclusions:

  • ALYREF upregulation is linked to malignant transformation in both canine mammary tumors and human breast cancer.
  • ALYREF influences cell viability, growth, and apoptosis by regulating EZH2, a key epigenetic modifier.
  • This study highlights ALYREF as a potential therapeutic target in mammary cancers.