MicroRNA-155 targets the SKI gene in human melanoma cell lines

• Published in: Pigment cell and melanoma research 2011-06, Vol.24 (3), p.538-550
• Main Authors: Levati, Lauretta, Pagani, Elena, Romani, Sveva, Castiglia, Daniele, Piccinni, Eugenia, Covaciu, Claudia, Caporaso, Patrizia, Bondanza, Sergio, Antonetti, Francesca R., Bonmassar, Enzo, Martelli, Fabio, Alvino, Ester, D'Atri, Stefania
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; 3' Untranslated Regions - genetics; Apoptosis; cell growth; Cell Line, Tumor; Cell Proliferation; Data processing; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Gene Expression Regulation, Neoplastic; Gene silencing; Humans; Malignancy; Melanocytes; Melanoma; MicroRNAs - biosynthesis; MicroRNAs - genetics; miR-155; miRNA; Pigments; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; siRNA; SKI; Ski protein; small interfering RNAs; Transcription; Transfection; Tumorigenesis
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/j.1755-148X.2011.00857.x

Summary 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.