Abstract
The expression of small, non-coding RNA or microRNAs (miR), is frequently deregulated in human cancer, but how these pathways affect disease progression is still largely elusive. Here, we report on a miR, miR-296, which is progressively lost during tumor progression and correlates with metastatic disease in colorectal, breast, lung, gastric, parathyroid, liver and bile ducts cancers. Functionally, miR-296 controls a global cell motility gene signature in epithelial cells by transcriptionally repressing the cell polarity–cell plasticity module, Scribble (Scrib). In turn, loss of miR-296 causes aberrantly increased and mislocalized Scrib in human tumors, resulting in exaggerated random cell migration and tumor cell invasiveness. Re-expression of miR-296 in MDA-MB231 cells inhibits tumor growth in vivo. Finally, miR-296 or Scrib levels predict tumor relapse in hepatocellular carcinoma patients. These data identify miR-296 as a global repressor of tumorigenicity and uncover a previously unexplored exploitation of Scrib in tumor progression in humans.
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Acknowledgements
We thank Riccardo Ghidoni, Michele Samaja and Massimo Locati for availability of laboratory equipment and reagents, Patrizia Doi and Delfina Tosi for technical help. AF is supported by a fellowship of the Doctorate School of Molecular Medicine at Università degli Studi di Milano. This work was supported by grants from the Fondazione Invernizzi (to GC), Fondazione Berlucchi (to SB), and from National Institutes of Health grants HL54131, CA140043, CA78810 and CA118005 (to DCA).
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Vaira, V., Faversani, A., Dohi, T. et al. miR-296 regulation of a cell polarity–cell plasticity module controls tumor progression. Oncogene 31, 27–38 (2012). https://doi.org/10.1038/onc.2011.209
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DOI: https://doi.org/10.1038/onc.2011.209
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