The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis

被引：806

作者：

Huang, Qihong ^{[1
]}

Gumireddy, Kiranmai ^{[1
]}

Schrier, Mariette ^{[2
]}

Le Sage, Carlos ^{[2
]}

Nagel, Remco ^{[2
]}

Nair, Suresh ^{[2
]}

Egan, David A. ^{[3
]}

Li, Anping ^{[1
]}

Huang, Guanghua ^{[1
]}

Klein-Szanto, Andres J. ^{[4
]}

Gimotty, Phyllis A. ^{[5
]}

Katsaros, Dionyssios ^{[6
]}

Coukos, George ^{[7
,8
,9
]}

Zhang, Lin ^{[7
,8
]}

Pure, Ellen ^{[1
]}

Agami, Reuven ^{[2
]}

机构：

[1] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA

[2] Netherlands Canc Inst, Div Tumor Biol, Amsterdam, Netherlands

[3] Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands

[4] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA

[5] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[6] Univ Turin, Dept Obstet & Gynecol, Turin, Italy

[7] Univ Penn, Ctr Res Early Detect & Cure Ovarian Ctr, Philadelphia, PA 19104 USA

[8] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA

[9] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

来源：

NATURE CELL BIOLOGY | 2008年 / 10卷 / 02期

关键词：

D O I：

10.1038/ncb1681

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

MicroRNAs ( miRNAs) are single-stranded, noncoding RNAs that are important in many biological processes(1,2). Although the oncogenic and tumour-suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumour metastasis was addressed only recently(3) and still remains largely unexplored(4,5). To identify potential metastasis-promoting miRNAs, we set up a genetic screen using a nonmetastatic, human breast tumour cell line that was transduced with a miRNA-expression library and subjected to a trans-well migration assay. We found that human miR-373 and miR-520c stimulated cancer cell migration and invasion in vitro and in vivo, and that certain cancer cell lines depend on endogenous miR-373 activity to migrate efficiently. Mechanistically, the migration phenotype of miR-373 and miR-520c can be explained by suppression of CD44. We found significant upregulation of miR-373 in clinical breast cancer metastasis samples that correlated inversely with CD44 expression. Taken together, our findings indicate that miRNAs are involved in tumour migration and invasion, and implicate miR-373 and miR-520c as metastasis-promoting miRNAs.

引用

页码：202 / U83

页数：24

共 37 条

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