MiR-502/SET8 regulatory circuit in pathobiology of breast cancer

Ben Liu1, Xining Zhang1, Fengju Song1

  • 1Department of Epidemiology and Biostatistics, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

Cancer Letters
|April 16, 2016
PubMed

Insights

MicroRNA-502 directly targets SET8 in breast cancer, suppressing tumor growth and improving survival. This miR-502/SET8 circuit offers a potential therapeutic target for cancer treatment.

Area of Science:

  • Molecular Oncology
  • Epigenetics
  • Cancer Biology

Background:

  • Previous research suggested miR-502 targets H4K20 methyltransferase SET8 in various cancers.
  • Direct targeting and clinical significance of the miR-502/SET8 regulatory circuit remained unclear.

Purpose of the Study:

  • To confirm SET8 as a direct target of miR-502.
  • To investigate the clinical significance of the miR-502/SET8 regulatory circuit in breast cancer.

Main Methods:

  • Cell-based experiments were performed.
  • Clinical studies analyzed 279 breast cancer samples.
  • Expression levels of miR-502 and SET8 were correlated with clinical outcomes.

Main Results:

  • SET8 was confirmed as a direct target of miR-502.
  • miR-502 treatment or SET8 downregulation inhibited cell proliferation, migration, invasion, and EMT.
  • miR-502 was downregulated in tumor tissues and inversely correlated with SET8.
  • High SET8 expression correlated with poor overall survival (OS) and disease-free survival (DFS).
  • Low miR-502/SET8 mRNA ratio associated with poor OS.

Conclusions:

  • The miR-502/SET8 regulatory circuit is a key player in breast cancer pathobiology.
  • This circuit represents a potential therapeutic target for intervention in cancer.

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