title: MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells.
abstract: miRNAs act as oncogenes or tumor suppressors in a wide variety of human cancers, including prostate cancer (PCa). We found a severe and consistent downregulation of miRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 region in metastatic cell lines as compared with normal prostatic epithelial cells (PrEC). In specimens of human prostate (28 normals, 99 primary tumors and 13 metastases), lower miRNA levels correlated significantly with a higher incidence of metastatic events and higher prostate specific antigen (PSA) levels, with similar trends observed for lymph node invasion and the Gleason score. We transiently transfected 10 members of the 14q32.31 cluster in normal prostatic epithelial cell lines and characterized their affect on malignant cell behaviors, including proliferation, apoptosis, migration and invasion. Finally, we identified FZD4, a gene important for epithelial-to-mesenchymal transition in (PCa), as a target of miR-377.
authors.affiliation: 1] University of Tor Vergata, Department Experimental Medicine and Surgery, Rome, Italy [2] IDI-IRCCS, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Formosa
authors.affiliation: The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Markert
authors.affiliation: University of Tor Vergata, Department Experimental Medicine and Surgery, Rome, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Lena
authors.affiliation: University of Tor Vergata, Department Experimental Medicine and Surgery, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Italiano
authors.affiliation: University of Tor Vergata, Department Experimental Medicine and Surgery, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Finazzi-Agro'
authors.affiliation: The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Levine
authors.affiliation: University of Tor Vergata, Department Experimental Medicine and Surgery, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bernardini
authors.affiliation: Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, Petersburg, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Garabadgiu
authors.affiliation: 1] University of Tor Vergata, Department Experimental Medicine and Surgery, Rome, Italy [2] IDI-IRCCS, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.affiliation: University of Tor Vergata, Department Experimental Medicine and Surgery, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Candi
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002883:Chromosomes, Human, Pair 14; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D051157:Frizzled Receptors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011467:Prostate / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012016:Reference Values
chemical_list: C402930:FZD4 protein, human; D051157:Frizzled Receptors; C534063:MIRN377 microRNA, human; D035683:MicroRNAs