miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells

• Published in: PloS one 2015-07, Vol.10 (7), p.e0131350-e0131350
• Main Authors: Mine, Mariko, Yamaguchi, Kojiro, Sugiura, Tsuyoshi, Chigita, Satomi, Yoshihama, Naoya, Yoshihama, Rumi, Hiyake, Naomi, Kobayashi, Yosuke, Mori, Yoshihide
• Format: Article
• Language: English
• Subjects: beta Catenin - genetics; beta Catenin - metabolism; Cell adhesion & migration; Cell Line, Tumor; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell migration; Cell Movement; Colorectal cancer; Comparative analysis; Epithelial Cells - metabolism; Epithelial Cells - pathology; Esophagus; Frizzled protein; Frizzled Receptors - genetics; Frizzled Receptors - metabolism; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Infection; Inhibition; Isoforms; Kangai-1 Protein - genetics; Kangai-1 Protein - metabolism; Kinases; Ligands; Lung - metabolism; Lung - pathology; Lung cancer; Lung carcinoma; Maxillofacial surgery; Medical prognosis; Melanoma; Metastases; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Miranda; miRNA; mRNA; Oligonucleotides, Antisense - genetics; Oligonucleotides, Antisense - metabolism; Phosphorylation; Plasmids - chemistry; Plasmids - metabolism; Polyclonal antibodies; Protein folding; Proteins; Science; Signal transduction; Signaling; Skin cancer; Surgery; Transfection; Wnt protein; Wnt Signaling Pathway; β-Catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131350

CD82/KAI1, a member of the tetraspanin superfamily, is a suppressor of metastasis and CD82 inhibits canonical Wnt signaling via downregulation of several Frizzled (FZD) isoforms, resulting in accumulation of β-catenin at the cell membrane. In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs). The miRanda algorithm predicted 11 miRNAs from FZD sequences. Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells. Transfection with miR-203 and miR338-3p mimics or inhibitors revealed that miR-203 downregulated FZD2 mRNA (by 0.268-fold) and protein expression (by 0.701-fold). Moreover, transfection with the miR-203 mimic also inhibited cell migration. Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway.