title: MicroRNA-155 targets the SKI gene in human melanoma cell lines.
abstract: The SKI protein is a transcriptional coregulator over-expressed in melanoma. Experimentally induced down-regulation of SKI inhibits melanoma cell growth in vitro and in vivo. MicroRNAs (miRNAs) negatively modulate gene expression and have been implicated in oncogenesis. We previously showed that microRNA-155 (miR-155) is down-regulated in melanoma cells as compared with normal melanocytes and that its ectopic expression impairs proliferation and induces apoptosis. Here, we investigated whether miR-155 could mediate melanoma growth inhibition via SKI gene silencing. Luciferase reporter assays demonstrated that miR-155 interacted with SKI 3'UTR and impaired gene expression. Transfection of melanoma cells with miR-155 reduced SKI levels, while inhibition of endogenous miR-155 up-regulated SKI expression. Specifically designed small interfering RNAs reduced SKI expression and inhibited proliferation. However, melanoma cells over-expressing a 3'UTR-deleted SKI were still susceptible to the antiproliferative effect of miR-155. Our data demonstrate for the first time that SKI is a target of miR-155 in melanoma. However, impairment of SKI expression is not the leading mechanism involved in the growth-suppressive effect of miR-155 found in this malignancy.
authors.affiliation: Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, Via dei Monti di Creta, Rome, Italy.
authors.forename: Lauretta
authors.initials: L
authors.lastname: Levati
authors.forename: Elena
authors.initials: E
authors.lastname: Pagani
authors.forename: Sveva
authors.initials: S
authors.lastname: Romani
authors.forename: Daniele
authors.initials: D
authors.lastname: Castiglia
authors.forename: Eugenia
authors.initials: E
authors.lastname: Piccinni
authors.forename: Claudia
authors.initials: C
authors.lastname: Covaciu
authors.forename: Patrizia
authors.initials: P
authors.lastname: Caporaso
authors.forename: Sergio
authors.initials: S
authors.lastname: Bondanza
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Antonetti
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonmassar
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
authors.forename: Ester
authors.initials: E
authors.lastname: Alvino
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Atri
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; C060614:SKI protein, human