Letter abstract
Nature Cell Biology 10, 202 - 210 (2008)
Published online: 13 January 2008 | doi:10.1038/ncb1681
The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis
Qihong Huang1,10, Kiranmai Gumireddy1,10, Mariette Schrier2,10, Carlos le Sage2, Remco Nagel2, Suresh Nair2, David A. Egan3, Anping Li1, Guanghua Huang1, Andres J. Klein-Szanto4, Phyllis A. Gimotty5, Dionyssios Katsaros6, George Coukos7,8,9, Lin Zhang7,8, Ellen Puré1 & Reuven Agami2
MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that are important in many biological processes1, 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 recently3 and still remains largely unexplored4, 5. To identify potential metastasis-promoting miRNAs, we set up a genetic screen using a non-metastatic, 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.
- The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
- Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia 19111-2497, USA.
- Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
- Department of Obstetrics and Gynecology, University of Turin, Turin, Italy.
- Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, PA 19104, USA.
- Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA.
- Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
- These authors contributed equally to this work
Correspondence to: Qihong Huang1,10 e-mail: qhuang@wistar.org
Correspondence to: Reuven Agami2 e-mail: r.agami@nki.nl
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