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Updated: Mar 22, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
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.
Abstract:
Our previous research and extensive epidemiological studies reproducibly demonstrated that miR-502 potentially targeted the expression of H4K20 methyltransferase SET8 in a wide spectrum of cancer. Yet, the direct targeting of SET8 by miR-502 has not been definitively proven. The clinical significance of the miR-502/SET8 regulatory circuit is also not clear. Here, we conducted cell-based experiments and clinical studies in a cohort of 279 breast cancer samples. We provide evidence that SET8 is a direct target of miR-502. Treatment with miR-502 or downregulation of SET8 suppressed cell proliferation and cell cycle, and reduced cell migration, invasion and EMT. Clinical analyses showed the miR-502 expression was lower in tumor tissues than in adjacent non-tumor tissues and had a significant inverse correlation with that of SET8. Furthermore, high expression of SET8 was significantly associated with poor overall survival (OS) and disease free survival (DFS) of breast cancer. The low expression ratio of miR-502 to SET8 mRNA was also significantly associated with poor OS. Thus, the miR-502/SET8 regulatory circuit emerges as a key regulator of the pathobiology of cancer and a focal point for possible therapeutic intervention.
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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