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

被引：45

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

来源：

ONCOTARGET | 2015年 / 6卷 / 06期

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

页码：3709 / 3721

页数：13

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