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Cancer Res. 2014 Nov 15;74(22):6648-60. doi: 10.1158/0008-5472.CAN-13-3710. Epub 2014 Sep 12.

MicroRNA100 inhibits self-renewal of breast cancer stem-like cells and breast tumor development.

Author information

1
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.
2
Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
3
Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
4
Division of Molecular Medicine and Genetics, Department of Internal Medicine and Life Sciences Institute, University of Michigan, Ann Arbor, Michigan.
5
Departments of Molecular Biosciences and Radiation Oncology, University of Kansas Cancer Center, University of Kansas Medical School, University of Kansas, Lawrence, Kansas.
6
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.
7
Cold Spring Harbor Laboratory, Program in Genetics and Bioinformatics, Cold Spring Harbor, New York, New York.
8
Department of Colorectal Surgery, Sixth Hospital of Sun Yat-sen University, Guangzhou, China.
9
Department of Breast Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
10
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.

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.

PMID:
25217527
PMCID:
PMC4370193
DOI:
10.1158/0008-5472.CAN-13-3710
[Indexed for MEDLINE]
Free PMC Article

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