title: 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.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yu
authors.forename: Peiwei
authors.initials: P
authors.lastname: Huangyang
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Ruorong
authors.initials: R
authors.lastname: Yan
authors.forename: Hongti
authors.initials: H
authors.lastname: Jia
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
authors.forename: Luyang
authors.initials: L
authors.lastname: Sun
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D004249:DNA Damage; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C549242:MIRN7-1 microRNA, human; C470730:KMT5A protein, human
keywords: Breast Cancer; DNA Damage; DNA Damage Response; Epithelial Mesenchymal Transition; MicroRNA; MicroRNA-7; SET8