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.
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ABSTRACT: The purpose of this study was to explore the functional role and mechanism of miR-155 in the development of renal cell carcinoma (RCC). miR-155 expression was quantified in renal cancers, matched adjacent non‑tumor tissues and renal cell lines using quantitative real-time PCR (RT-PCR). Cell proliferation, apoptosis and migratory activity were measured following suppression of miR-155 expression by antisense oligonucleotides. miR-155 targets were scanned using target prediction programs. Following the inhibition of miR-155, target gene expression was detected by western blotting. The expression of miR-155 was upregulated in clear cell RCC (ccRCC) tissue and renal cancer cell lines. The suppression of miR-155 inhibited cell proliferation and migratory activity and induced apoptosis in renal cancer cells. The suppressor gene suppressor of cytokine signaling (SOCS-1) and BACH1 were predicted as potential target genes by bioinformatics analysis. The suppression of miR-155 inhibited BACH1 protein expression. miR-155 may function as an oncogene by targeting BACH1. Thus, the inhibition of miR-155 may be an effective way to treat RCC.Molecular Medicine Reports 04/2012; 5(4):949-54. · 1.17 Impact Factor