Journal
CANCER LETTERS
Volume 376, Issue 2, Pages 259-267Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.04.008
Keywords
Breast cancer; miR-502; SET8; Cell cycle; Epithelial to mesenchymal transition
Categories
Funding
- National Natural Science Foundation of China [81172762, 81071627, 81572445, 81202275, 81473039]
- program for the Tianjin City High School Science &Technology Fund Planning Project [20090137]
- Program for Changjiang Scholars and Innovative Research Team in University in China [IRT_14R40]
- Chinese 863 Program [2012AA02A207]
- National Key Scientific and Technological Project [2015BAI12B15]
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Our previous research and extensive epidemiological studies reproducibly demonstrated that miR-502 potentially targeted the expression of H4K20 methyltransferase SETS in a wide spectrum of cancer. Yet, the direct targeting of SETS 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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