microRNA-7 suppresses the invasive potential of breast cancer cells and sensitizes cells to DNA damages by targeting histone methyltransferase SET8.

Abstract	SET8 (SET domain containing 8) is a histone H4 lysine 20 (H4K20)-specific monomethyltransferase in higher eukaryotes that exerts diverse functions in transcription regulation, DNA repair, tumor metastasis, and genome integrity. The activity of SET8 is tightly controlled during cell cycle through post-translational modifications, including ubiquitination, phosphorylation, and sumoylation. However, how the expression of SET8 is regulated is not fully understood. Here, we report that microRNA-7 is a negative regulator of SET8. We demonstrated that microRNA-7 inhibits H4K20 monomethylation and suppresses epithelial-mesenchymal transition and the invasive potential of breast cancer cells. We showed that microRNA-7 promotes spontaneous DNA damages and sensitizes cells to induced DNA damages. Our experiments provide a molecular mechanism for the regulation of SET8 and extend the biological function of microRNA-7 to DNA damage response, supporting the pursuit of microRNA-7 as a potential target for breast cancer intervention.
Authors	Na Yu, Peiwei Huangyang, Xiaohan Yang, Xiao Han, Ruorong Yan, Hongti Jia, Yongfeng Shang, Luyang Sun
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 288 Issue 27 Pg. 19633-42 (Jul 05 2013) ISSN: 1083-351X [Electronic] United States
PMID	23720754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Histones MIRN7 microRNA, human MicroRNAs Neoplasm Proteins RNA, Neoplasm Histone-Lysine N-Methyltransferase KMT5A protein, human
Topics	Animals Breast Neoplasms (genetics, metabolism, pathology, prevention & control) Cell Line, Tumor DNA Damage Epithelial-Mesenchymal Transition (genetics) Female Histone-Lysine N-Methyltransferase (genetics, metabolism) Histones (genetics, metabolism) Humans Methylation MicroRNAs (genetics, metabolism) Neoplasm Invasiveness Neoplasm Proteins (genetics, metabolism) RNA, Neoplasm (genetics, metabolism)

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