title: miR-296 regulation of a cell polarity-cell plasticity module controls tumor progression.
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.
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Vaira
authors.forename: A
authors.initials: A
authors.lastname: Faversani
authors.forename: T
authors.initials: T
authors.lastname: Dohi
authors.forename: M
authors.initials: M
authors.lastname: Montorsi
authors.forename: C
authors.initials: C
authors.lastname: Augello
authors.forename: S
authors.initials: S
authors.lastname: Gatti
authors.forename: G
authors.initials: G
authors.lastname: Coggi
authors.forename: D C
authors.initials: DC
authors.lastname: Altieri
authors.forename: S
authors.initials: S
authors.lastname: Bosari
mesh_terms: D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C549871:MIRN296 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins