Abstract
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.
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Acknowledgements
We would like to thank Janet Price (The University of Texas, MD Anderson Cancer Center, Houston, TX) for providing the MDA-MB-435 cell line, Ron Kerkhoven and Mike Heimerikx (Netherlands Cancer Institute, Amsterdam) for assistance in using the array facility, Roderick Beijersbergen (Netherlands Cancer Institute, Amsterdam) for establishing the high-throughput-screening facility and Louise Showe, Celia Chang and Wenhai Horng (The Wistar Institute) for microarray analysis. Q.H. is supported by Breast Cancer Alliance, Pardee Foundation, V Foundation and Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health. R.A. is supported by the Dutch Cancer Society (KWF), the European Young Investigator Award (EURYI), the Dr Josef Steiner Cancer Research Foundation and the EMBO Young Investigator Program. G.C. and L.Z. are supported by the Netherlands Cancer Institute Ovarian Cancer Research fund and the American Cancer Society.
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Huang, Q., Gumireddy, K., Schrier, M. et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 10, 202–210 (2008). https://doi.org/10.1038/ncb1681
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DOI: https://doi.org/10.1038/ncb1681
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