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

被引:44
作者
Ke, Jia [1 ]
Zhao, Zhiju [2 ,3 ]
Hong, Su-Hyung [4 ]
Bai, Shoumin [5 ]
He, Zhen [1 ]
Malik, Fayaz [6 ]
Xu, Jiahui [2 ,3 ]
Zhou, Lei [2 ,3 ]
Chen, Weilong [2 ,3 ]
Martin-Trevino, Rachel [6 ]
Wu, Xiaojian [1 ]
Lan, Ping [1 ]
Yi, Yongju [7 ]
Ginestier, Christophe [8 ]
Ibarra, Ingrid [9 ]
Shang, Li [6 ]
McDermott, Sean [6 ]
Luther, Tahra [6 ]
Clouthier, Shawn G. [6 ]
Wicha, Max S. [6 ]
Liu, Suling [2 ,3 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510275, Guangdong, Peoples R China
[2] Univ Sci & Technol China, Innovat Ctr Cell Biol, Hefei 230026, Anhui, Peoples R China
[3] Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, Sch Life Sci & Med Ctr, Hefei 230026, Anhui, Peoples R China
[4] Kyungpook Natl Univ, Sch Dent, Dept Oral Microbiol, Daegu, South Korea
[5] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Oncol, Guangzhou 510275, Guangdong, Peoples R China
[6] Univ Michigan, Dept Internal Med, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA
[7] Sun Yat Sen Univ, Affiliated Hosp 6, Network Informat Ctr, Guangzhou 510275, Guangdong, Peoples R China
[8] Univ Aix Marseille 2, Inst Paoli Calmettes, Inserm UMR891, Ctr Rech Cancerol Marseille,Lab Oncol Mol, Marseille, France
[9] Cold Spring Harbor Lab, Program Genet & Bioinformat, Cold Spring Harbor, NY 11724 USA
关键词
miR-221; breast stem-like cells; differentiation; hierarchy; ADULT HUMAN BREAST; IN-VITRO; BASAL; SUBPOPULATIONS; PREDICTOR; SURVIVAL; SUBTYPES; MIR-221; MARKER; LINES;
D O I
10.18632/oncotarget.2888
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 knockdown 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.
引用
收藏
页码:3709 / 3721
页数:13
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