title: MiR-502/SET8 regulatory circuit in pathobiology of breast cancer.
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.
authors.affiliation: Department 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.
authors.forename: Ben
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department 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.
authors.forename: Xining
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department 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.
authors.forename: Fengju
authors.initials: F
authors.lastname: Song
authors.affiliation: Department 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department 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.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department 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.
authors.forename: Haixin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department 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.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA. Electronic address: wzhang@mdanderson.org.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department 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. Electronic address: chenkexin@tjmuch.com.
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D059447:Cell Cycle Checkpoints; D002465:Cell Movement; D049109:Cell Proliferation; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D034622:RNA Interference; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C545730:MIRN502 microRNA, human; D035683:MicroRNAs; D011495:Histone-Lysine N-Methyltransferase; C470730:KMT5A protein, human
keywords: Breast cancer; Cell cycle; Epithelial to mesenchymal transition; SET8; miR-502