title: Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells.
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.
authors: Department of Colorectal Surgery, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors: Jia
authors: J
authors: Ke
authors: 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.
authors: Zhiju
authors: Z
authors: Zhao
authors: Department of Oral Microbiology, School of Dentistry Kyungpook National University, Jung-gu, Daegu, South Korea.
authors: Su-Hyung
authors: SH
authors: Hong
authors: Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, China.
authors: Shoumin
authors: S
authors: Bai
authors: Department of Colorectal Surgery, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors: Zhen
authors: Z
authors: He
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Fayaz
authors: F
authors: Malik
authors: 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.
authors: Jiahui
authors: J
authors: Xu
authors: 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.
authors: Lei
authors: L
authors: Zhou
authors: 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.
authors: Weilong
authors: W
authors: Chen
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Rachel
authors: R
authors: Martin-Trevino
authors: Department of Colorectal Surgery, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors: Xiaojian
authors: X
authors: Wu
authors: Department of Colorectal Surgery, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors: Ping
authors: P
authors: Lan
authors: Network Information Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors: Yongju
authors: Y
authors: Yi
authors: Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 Inserm/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France.
authors: Christophe
authors: C
authors: Ginestier
authors: Cold Spring Harbor Laboratory, Program in Genetics and Bioinformatics, Cold Spring Harbor, NY, USA.
authors: Ingrid
authors: I
authors: Ibarra
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Li
authors: L
authors: Shang
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Sean
authors: S
authors: McDermott
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Tahra
authors: T
authors: Luther
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Shawn G
authors: SG
authors: Clouthier
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Max S
authors: MS
authors: Wicha
authors: 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.
authors: Suling
authors: S
authors: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D035683:MicroRNAs; C525709:MIR221, human