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Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells

2015; Impact Journals LLC; Volume: 6; Issue: 6 Linguagem: Inglês

10.18632/oncotarget.2888

1949-2553

Jia Ke, Zhiju Zhao, Su-Hyung Hong, Shoumin Bai, Zhen He, Fayaz Malik, Jiahui Xu, Lei Zhou, Weilong Chen, Rachel Martin-Trevino, Xiaojian Wu, Ping Lan, Yongju Yi, Christophe Ginestier, Ingrid Ibarra, Shang Li, Sean McDermott, Tahra Luther, Shawn G. Clouthier, Max S. Wicha, Suling Liu,

Cancer Cells and Metastasis

// Jia Ke 1,* , Zhiju Zhao 2,* , Su-Hyung Hong 3 , Shoumin Bai 4 , Zhen He 1 , Fayaz Malik 5 , Jiahui Xu 2 , Lei Zhou 2 , Weilong Chen 2 , Rachel Martin-Trevino 5 , Xiaojian Wu 1 , Ping Lan 1 , Yongju Yi 6 , Christophe Ginestier 7 , Ingrid Ibarra 8 , Li Shang 5 , Sean McDermott 5 , Tahra Luther 5 , Shawn G. Clouthier 5 , Max S. Wicha 5 , Suling Liu 2 1 Department of Colorectal Surgery, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 2 Innovation Center for Cell Biology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China 3 Department of Oral Microbiology, School of Dentistry Kyungpook National University, Jung-gu, Daegu, South Korea 4 Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, China 5 Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA 6 Network Information Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 7 Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 Inserm/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France 8 Cold Spring Harbor Laboratory, Program in Genetics and Bioinformatics, Cold Spring Harbor, NY, USA * These authors have contributed equally to this work Correspondence to: Suling Liu, e-mail: suling@ustc.edu.cn Max S. Wicha, e-mail: mwicha@med.umich.edu Jia Ke, e-mail: 278494686@qq.com Keywords: miR-221, breast stem-like cells, differentiation, hierarchy Received: September 10, 2014 Accepted: December 09, 2014 Published: February 17, 2015 ABSTRACT Increasing evidence suggests that lineage specific subpopulations and stem-like cells exist in normal and malignant breast tissues. Epigenetic mechanisms maintaining this hierarchical homeostasis remain to be investigated. In this study, we found the level of microRNA221 (miR-221) was higher in stem-like and myoepithelial cells than in luminal cells isolated from normal and malignant breast tissue. In normal breast cells, over-expression of miR-221 generated more myoepithelial cells whereas knock-down of miR-221 increased luminal cells. Over-expression of miR-221 stimulated stem-like cells in luminal type of cancer and the miR-221 level was correlated with clinical outcome in breast cancer patients. Epithelial-mesenchymal transition (EMT) was induced by overexpression of miR-221 in normal and breast cancer cells. The EMT related gene ATXN1 was found to be a miR-221 target gene regulating breast cell hierarchy. In conclusion, we propose that miR-221 contributes to lineage homeostasis of normal and malignant breast epithelium.