title: miR-205 Exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon.
abstract: Limited information is available concerning the expression and role of microRNAs in prostate cancer. In this study, we investigated the involvement of miR-205 in prostate carcinogenesis. Significantly lower miR-205 expression levels were found in cancer than in normal prostate cell lines as well as in tumor compared with matched normal prostate tissues, with a particularly pronounced reduction in carcinomas from patients with local-regionally disseminated disease. Restoring the expression of miR-205 in prostate cancer cells resulted in cell rearrangements consistent with a mesenchymal-to-epithelial transition, such as up-regulation of E-cadherin and reduction of cell locomotion and invasion, and in the down-regulation of several oncogenes known to be involved in disease progression (i.e., interleukin 6, caveolin-1, EZH2). Our evidence suggests that these events are driven by the concurrent repression of specific predicted miR-205 targets, namely N-chimaerin, ErbB3, E2F1, E2F5, ZEB2, and protein kinase Cepsilon. Strikingly, the latter seemed to play a direct role in regulating epithelial-to-mesenchymal transition. In fact, its down-regulation led to a cell phenotype largely reminiscent of that of cells ectopically expressing miR-205. Overall, we showed for the first time that miR-205 exerts a tumor-suppressive effect in human prostate by counteracting epithelial-to-mesenchymal transition and reducing cell migration/invasion, at least in part through the down-regulation of protein kinase Cepsilon.
authors.affiliation: Department of Experimental Oncology and Laboratories, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gandellini
authors.forename: Marco
authors.initials: M
authors.lastname: Folini
authors.forename: Nicole
authors.initials: N
authors.lastname: Longoni
authors.forename: Marzia
authors.initials: M
authors.lastname: Pennati
authors.forename: Mara
authors.initials: M
authors.lastname: Binda
authors.forename: Maurizio
authors.initials: M
authors.lastname: Colecchia
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvioni
authors.forename: Rosanna
authors.initials: R
authors.lastname: Supino
authors.forename: Roberta
authors.initials: R
authors.lastname: Moretti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Limonta
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdagni
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D004847:Epithelial Cells / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051744:Protein Kinase C-epsilon / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger; D012097:Repressor Proteins; D000074165:Zinc Finger E-box Binding Homeobox 2; C534425:MIR205, human; C492363:ZEB2 protein, human