title: MicroRNA100 inhibits self-renewal of breast cancer stem-like cells and breast tumor development.
abstract: miRNAs are essential for self-renewal and differentiation of normal and malignant stem cells by regulating the expression of key stem cell regulatory genes. Here, we report evidence implicating the miR100 in self-renewal of cancer stem-like cells (CSC). We found that miR100 expression levels relate to the cellular differentiation state, with lowest expression in cells displaying stem cell markers. Utilizing a tetracycline-inducible lentivirus to elevate expression of miR100 in human cells, we found that increasing miR100 levels decreased the production of breast CSCs. This effect was correlated with an inhibition of cancer cell proliferation in vitro and in mouse tumor xenografts due to attenuated expression of the CSC regulatory genes SMARCA5, SMARCD1, and BMPR2. Furthermore, miR100 induction in breast CSCs immediately upon their orthotopic implantation or intracardiac injection completely blocked tumor growth and metastasis formation. Clinically, we observed a significant association between miR100 expression in breast cancer specimens and patient survival. Our results suggest that miR100 is required to direct CSC self-renewal and differentiation.
authors.affiliation: 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 and Technology of China, Hefei, Anhui, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Deng
authors.affiliation: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Li
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shoumin
authors.initials: S
authors.lastname: Bai
authors.affiliation: 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 and Technology of China, Hefei, Anhui, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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 and Technology of China, Hefei, Anhui, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: He
authors.affiliation: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Rachel
authors.initials: R
authors.lastname: Martin-Trevino
authors.affiliation: Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine and Life Sciences Institute, University of Michigan, Ann Arbor, Michigan.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Departments of Molecular Biosciences and Radiation Oncology, University of Kansas Cancer Center, University of Kansas Medical School, University of Kansas, Lawrence, Kansas.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Meng
authors.affiliation: 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 and Technology of China, Hefei, Anhui, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: 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 and Technology of China, Hefei, Anhui, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sean P
authors.initials: SP
authors.lastname: McDermott
authors.affiliation: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Alexa E
authors.initials: AE
authors.lastname: Ariazi
authors.affiliation: Centre de Recherche en Cance'rologie de Marseille, Laboratoire d'Oncologie Mole'culaire, UMR891 Inserm/Institut Paoli-Calmettes, Universite' de la Me'diterrane'e, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.affiliation: Cold Spring Harbor Laboratory, Program in Genetics and Bioinformatics, Cold Spring Harbor, New York, New York.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ibarra
authors.affiliation: Department of Colorectal Surgery, Sixth Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Ke
authors.affiliation: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Tahra
authors.initials: T
authors.lastname: Luther
authors.affiliation: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Clouthier
authors.affiliation: Departments of Molecular Biosciences and Radiation Oncology, University of Kansas Cancer Center, University of Kansas Medical School, University of Kansas, Lawrence, Kansas.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: 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 and Technology of China, Hefei, Anhui, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Shan
authors.affiliation: Department of Breast Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Erwei
authors.initials: E
authors.lastname: Song
authors.affiliation: Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Herui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Cold Spring Harbor Laboratory, Program in Genetics and Bioinformatics, Cold Spring Harbor, New York, New York.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine and Life Sciences Institute, University of Michigan, Ann Arbor, Michigan.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Weiss
authors.affiliation: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
authors.affiliation: 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 and Technology of China, Hefei, Anhui, China. suling@ustc.edu.cn.
authors.forename: Suling
authors.initials: S
authors.lastname: Liu
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology; D000444:Aldehyde Dehydrogenase / Q000032:analysis; D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000502:physiology; D001943:Breast Neoplasms / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C544266:MIRN100 microRNA, human; D035683:MicroRNAs; C109786:SMARCD1 protein, human; D014157:Transcription Factors; D000444:Aldehyde Dehydrogenase; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human