title: MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha.
abstract: The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3'-untranslated region (3'UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Ke-Di
authors.initials: KD
authors.lastname: Sa
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Lin-Tao
authors.initials: LT
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: An-Gang
authors.initials: AG
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi'an, China. Electronic address: ruizhang@fmmu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: jingfan@fmmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi'an, China; Department of Otolaryngology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. Electronic address: kakamax85@hotmail.com.
authors.forename: Ka
authors.initials: K
authors.lastname: Bian
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human
keywords: Breast cancer; Proliferation; TOP2a; microRNA