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.

miR-296 regulation of a cell polarity-cell plasticity module controls tumor progression / V. Vaira, A. Faversani, T. Dohi, M. Montorsi, C. Augello, S. Gatti, G. Coggi, D.C. Altieri, S. Bosari. - In: ONCOGENE. - ISSN 0950-9232. - 31:1(2012), pp. 27-38.

miR-296 regulation of a cell polarity-cell plasticity module controls tumor progression

V. Vaira;A. Faversani;M. Montorsi;C. Augello;G. Coggi;S. Bosari
2012

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.
cell plasticity; metastases; miR-296; Scribble; tumor progression; Animals; Cell Movement; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Membrane Proteins; Mice; MicroRNAs; Neoplasms; Tumor Suppressor Proteins; Cell Polarity; Molecular Biology; Cancer Research; Genetics
Settore MED/18 - Chirurgia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/160258
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