miR-221/222 Promotes S-Phase Entry and Cellular Migration in Control of Basal-Like Breast Cancer
Yuan Li,
Chunli Liang,
Haizhong Ma,
Qian Zhao,
Ying Lu,
Zhendong Xiang,
Li Li,
Jie Qin,
Yihan Chen,
William C. Cho,
Richard G. Pestell,
Li Liang,
Zuoren Yu
Affiliations
Yuan Li
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
Chunli Liang
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
Haizhong Ma
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
Qian Zhao
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
Ying Lu
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
Zhendong Xiang
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
Li Li
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
Jie Qin
Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai 200120, China
Yihan Chen
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
William C. Cho
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
Richard G. Pestell
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
Li Liang
Lanzhou University School of Pharmacy, the First Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730000, China
Zuoren Yu
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
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.
