A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis
Author(s)Valastyan, Scott John; Reinhardt, Ferenc; Benaich, Nathan; Calogrias, Diana; Szász, Attila M.; Wang, Zhigang C.; Brock, Jane E.; Richardson, Andrea L.; Weinberg, Robert A.; Nathan Benaich; ... Show more Show less
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MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Valastyan, Scott, Ferenc Reinhardt, Nathan Benaich, Diana Calogrias, Attila M. Szász, Zhigang C. Wang, Jane E. Brock, Andrea L. Richardson, and Robert A. Weinberg. “A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis.” Cell 137, no. 6 (June 2009): 1032–1046. © 2009 Elsevier Inc.
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