title: miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer.
abstract: The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC.
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. liyuan_0806@hotmail.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. liang2006718@sina.com.
authors.forename: Chunli
authors.initials: C
authors.lastname: Liang
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. liangli418@163.com.
authors.forename: Haizhong
authors.initials: H
authors.lastname: Ma
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. tiankong74177@126.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. liyuan_0806@hotmail.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. druid456@msn.com.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. flylily322@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai 200120, China. shhqj@shmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. yihanchen@hotmail.com.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China. williamcscho@gmail.com.
authors.forename: William C
authors.initials: WC
authors.lastname: Cho
authors.affiliation: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. richard.pestell@jefferson.edu.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.affiliation: Lanzhou University School of Pharmacy, the First Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730000, China. liangli418@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. zuoren.yu@tongji.edu.cn.
authors.forename: Zuoren
authors.initials: Z
authors.lastname: Yu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000235:genetics / Q000502:physiology*
chemical_list: D035683:MicroRNAs; C525709:MIR221, human; C525710:MIR222, human