Png, K. J., Yoshida, M., Zhang, X. H. F., Shu, W., Lee, H., Rimner, A., Chan, T. A., Comen, E., Andrade, V. P., Kim, S. W., King, T. A., Hudis, C. A., Norton, L., Hicks, J. B., Massagué, J., Tavazoie, S. F. (February 2011) MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer. Genes and Development, 25 (3). pp. 226-231. ISSN 08909369
Abstract
Post-transcriptional regulators have emerged as robust effectors of metastasis and display deregulated expression through unknown mechanisms. Here, we reveal that the human microRNA-335 locus undergoes genetic deletion and epigenetic promoter hypermethylation in every metastatic derivative obtained from independent patients' malignant cell populations. Genetic deletion of miR-335 is a common event in human breast cancer, is enriched for in breast cancer metastases, and also correlates with ovarian cancer recurrence. We furthermore identify miR-335 as a robust inhibitor of tumor reinitiation. We thus implicate the miR-335 locus on 7q32.2 as the first selective metastasis suppressor and tumor initiation suppressor locus in human breast cancer. © 2011 by Cold Spring Harbor Laboratory Press.
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